Pulsed Doppler Determinations of Cardiac Output in Neonates: Normal Standards for Clinical Use

(1)

Pulsed

Doppler

Determinations

of Cardiac

Output

in Neonates:

Normal

Standards

for

Clinical

Use

Frans

J. Walther,

MD, PhD,

Bijan

Siassi,

MD, Naglaa

A. Ramadan,

MD,

Ananda

K. Ananda,

MD, and Paul V. K. Wu, MD

From the Neonatology Division, Department of Pediatrics, University of Southern California School of Medicine, Los Angeles County-USC Medical Center, Los Angeles

ABSTRACT.

Noninvasive monitoring of cardiac output can greatly facilitate the clinical assessment and man-agement of neonates with cardiovascular compromise. To assess normal values of cardiac output in neonates, mean blood flow velocity was measured in the ascending aorta from a suprasternal approach using a range-gated, pulsed

Doppler velocity meter, and aortic root diameter was

determined from an M-mode echocardiogram. These techniques were combined, and cardiac output was

eva!-uated in 59 healthy premature and 62 term newborn

infants during the first week of life. Birth weights ranged from 780 g to 4,740 g and gestational age from 27 to 42

weeks. Cardiac output values increased linearly with

ad-vancing birth weight (r = +.94,

P

< .001) and gestational age (r = +.95,

P

< .001). Mean cardiac output values (±SD) per kilogram of body weight were 249 ± 34 mL/

mm/kg and decreased with advancing birth weight: <1,500 g = 265 ± 32 mL/min/kg; 1,500 to 2,500 g = 253

± 34 mL/min/kg; and >2,500 g = 241 ± 33 mL/min/kg.

For clinical use, 325 mL/min/kg and 200 mL/min/kg can

be used as upper and lower limits of normal, respectively.

Doppler cardiac output estimates compared favorably

with studies using invasive techniques.

Pediatrics

1985; 76:829-833; cardiac output, neonate, pulsed Doppler tech-nique, echocardiography.

The combination of range-gated, pulsed Doppler

and

echocardiographic

techniques provides reliable

estimates of aortic root blood flow and of left

yen-tricular output which compare closely with the

“gold-standard”

Fick

principle

in infants

and

chil-dren.’3

Noninvasive

monitoring

of cardiac

output

can

greatly

facilitate

the

clinical

assessment

and

Received for publication July 30, 1984; accepted Dec 13, 1984. Dr Walther is a Fuibright research scholar.

Reprint requests to (F.J.W.) Department of Neonatology, Uni-versity of Limburg, P0 Box 616, 6200 MD Maastricht, The

Netherlands.

management of neonates with birth asphyxia,

hy-potensive shock, persistent fetal circulation, and assisted ventilation.4 Normal values of cardiac

out-put in relation to birth weight and gestational age

have

not

yet

been

established

using

this

method.

The purpose of this study was to estimate

Doppler-derived cardiac output in healthy premature and

term neonates.

MATERIALS

AND

METHODS

A total

of 121

healthy

premature

and

term

new-born infants admitted to the newborn nursery of

Women’s Hospital of Los Angeles County-Univer-sity of Southern California Medical Center were

studied. Informed parental consent was a

require-ment for the study. Within each 500-g birth weight

subgroup between 750 g and 4,750 g, at least 12 healthy newborn infants were selected for study

(Table).

All were

in a steady,

quiet

state

during

the

examination. Exclusion criteria were clinical,

echo-cardiographic, or radiographic evidence of

cardio-vascular or respiratory abnormalities, respiratory assistance, a hematocrit value below 45%, infants of mothers with diabetes mellitus, and infants with

a birth weight below the 10th percentile of the

Lubchenco curves.5 Premature neonates with

din-ical or echocardiographic evidence of a patent

duc-tus arteriosus were excluded from the study. Also

excluded were infants with left ventricular

myocar-dial dysfunction as diagnosed by M-mode

echocar-diography (Picker Echoview System 80C with a 5.0

MHz

or

7.5 MHz

transducer)

in

the

presence

of

abnormal left ventricular shortening fraction, left

ventricular systolic time interval and/or left atrial

to aortic ratio. Gestational age was estimated from

the first day of the mother’s last menstrual period

(2)

TABLE.

Cha

racte ristics of the S tudy Population* Wt Groups (g) n Birth Wt (g) Gesta-tional Age (wk) 5ex (M/F) Apgar

At 1 At 5

mm mm

Age at

Exami-nation (d)

Cardiac Output Aortic Diameter (cm) . mL/min . mL/min/kg

750-1,249 14 1,057 ± 154 27.9 ± 0.8 5/9 4.8 ± 2.1 7.1 ± 2.0 5.2 ± 2.8 275 ± 37 262 ± 31 0.68 ± 0.06 1,250-1,749 23 1,492 ± 151 30.9 ± 1.3 9/14 5.9 ± 2.2 8.2 ± 0.8 2.6 ± 0.6 388 ± 60 261 ± 36 0.76 ± 0.06

1,750-2,249 14 2,004 ± 139 33.6 ± 1.1 10/4 7.6 ± 1.4 8.5 ± 0.7 2.2 ± 1.0 522 ± 92 259 ± 35 0.86 ± 0.07

2,250-2,749 13 2,458 ± 158 35.8 ± 1.4 8/5 7.7 ± 1.7 8.5 ± 1.2 1.4 ± 0.8 602 ± 85 244 ± 27 0.91 ± 0.07 2,750-3,249 15 2,977 ± 164 39.6 ± 1.4 8/7 8.5 ± 0.5 9.0 ± 0 1.5 ± 0.9 737 ± 128 247 ± 37 1.00 ± 0.08

3,250-3,749 15 3,504 ± 160 41.1 ± 0.8 3/12 7.9 ± 1. 9.1 ± 0.5 1.8 ± 0.9 902 ± 120 257 ± 35 1.00 ± 0.07 3,750-4,249 15 4,033 ± 143 40.6 ± 1.2 8/7 7.7 ± 1.3 8.9 ± 0.5 1.3 ± 0.6 924 ± 119 229 ± 31 1.05 ± 0.06 4,250-4,750 12 4,468 ± 163 40.7 ± 0.9 8/4 8.0 ± 0.9 9.0 ± 0 1.4 ± 0.7 987 ± 67 221 ± 15 1.05 ± 0.05

Total 121 2,648 ± 1,141 35.9 ± 4.9 59/62 7.2 ± 1.9 8.5 ± 1.1 2.2 ± 1.7 645 ± 264 249 ± 34 0.90 ± 0.14

*Values are means ± 1 SD.

If there

was

a discrepancy

of more

than

2 weeks

between

the

estimated

ages

based

on the

last

men-strual period and the Ballard method, the latter

was used. Gestational age ranged from 27 to 42

weeks and birth weight from 780 g to 4,740 g. Age

at

study

ranged

from

24 to

72 hours

in newborns

weighing

more

than

1,250

g and

from

one

to eight

days in newborn infants weighing less than 1,250 g

(Table).

Blood

velocity

in the

ascending

aorta

was

mea-sured by using a 3.5-MHz,

range-gated,

pulsed-ultrasound Doppler velocity meter (Cardioflo TM,

Cardionics,

Houston).

A nonfocused,

6-mm

diame-ter

transducer

was

positioned

in the

suprasternal

notch

on

a layer

of airless

contact

gel.

It was

an-gulated

so that

the

ultrasound

beam

was

coaxially

aligned

as

closely

as

possible

with

the

ascending

aorta

and

was

directed

into

the

region

just

above

the aortic valve leaflets. Sample volume depth (1.5

cm

to

3.5 cm)

was

adjusted

for

maximum

systolic

velocity,

and

gain

control

was

reduced

until

the

diastolic jitter disappeared and the baseline was

approximately

flat.

The

highest

velocity

signals

obtained

during

30 to

60 cardiac

cycles

were

re-corded

on

a

strip

chart

recorder.

Zero-crossing

counter analysis provided the mean Doppler

fre-quency

shift.

The

mean

aortic

blood

flow

velocity

was calculated according to the Doppler equation:

V =

(1

x

c)/(2

X

F x cos

0),

where

V

=

velocity

in

centimeters

per

second,

f

=

frequency

shift

in Hertz,

C = speed of sound in blood,

F

=

frequency

of

transmitted ultrasound, and 0 =

angle

between

blood

flow

vector

and

ultrasound

beam.

Cos

0

was

assumed to be 1 as the angle of incidence is kept

between

0#{176}

± 15#{176}using a suprasternal approach.7

The

aortic

root

dimension

was

measured

on the

M-mode

echocardiogram

in early

diastole

with

lead-ing edge methodology,8 ie, from the anterior aortic

wall

to the

boundary

of the

posterior

wall

in an

area

that

visualized

centered

aortic

valvular

tissue to reduce the potential for angulation error.8

A minimum

of three

cardiac

cycles

were

measured,

and

mean

values

were

calculated

in hundredths

of

centimeters.

Cardiac

output

was

calculated

from

the

volumet-rid flow

equation:

Q

=

ir

X &/4 X V X 60,

where

Q

=

volumetric

flow

in

milliliters

per

minute,

d =

diameter

of the

aorta

in centimeters,

and

V =

mean

velocity

in centimeters

per

second.

All cardiac

out-put

calculations

assumed

an

aortic

diameter

of 1.0

cm and

were

recalculated

using

the

actual

diameter.

Cardiac

output

was

plotted

against

gestational

age and birth weight, and correlation coefficients

were

determined

by linear

regression

analysis.

Stu-dent’s t test was used to estimate the significance

of the

correlation

coefficients

and

the

differences

between

the

means

of two

samples.

All

values

are

given

as means

± 1

SD.

RESULTS

Fifty-nine

healthy

premature

and

62 term

infants

were

studied.

Cardiac

output

values

increased

grad-ually

with

increasing

birth

weight

(Fig

1),

with

a

correlation

coefficient

of

.94

(P

< .001). Mean

cardiac

output

per

kilogram

of body

weight

was

249

±

34 mL/min/kg

(Table)

and

decreased

slightly

with

increasing

birth

weight:

less

than

1,500

g (n

=

27) 265 ± 32

mL/min/kg,

from

1,500

to

2,500

g

(n =

31)

253 ± 34 mL/min/kg, and

greater

than

2,500 g (n =

63)

241

±

33 mL/min/kg

(Fig

2). The

difference

between

neonates

less

than

1,500

g and

(3)

esti-S C E E D a. p.. D 0 C.) a ‘C C.) LU -i a. a. 0 a :. . S 1000 800 600 400 200 Regression Line C E E I-. a. I-0 0 ‘C a ‘C 0 a: LU -J a. a. 0 a 1000 800 600 400 200 I S 8 n =121 y70.3+217.1 Cx) r O.4 a ₈

I n= 121

y=50.6 Cx)-1169.9 r 095

,

350 E 300 E

:

250 I-a. 200 0 0 ‘C a a: 100

t

95% 50%

Our

study

provides

normal

values

for

Doppler-derived

cardiac

output

in premature

and

term

new-born

infants

with

normal

cardiovascular

systems.

Prior

to this,

only

one

study

had

described

Doppler

cardiac

output

values

in healthy

neonates.9

Alver-son et al.9 reported cardiac output values of 221 ±

56 mL/min/kg in eight premature neonates and 236 ± 47

mL/min/kg

in

14 term

neonates

in the

first

week

of

life.

Our

results

are

comparable

to

those of Alverson’s in term newborn infants, but

they

differ

for

premature

neonates.

Our

data

con-firm

the

observation

of Wallgren

et

alio that

pre-mature

newborns

without

cardiovascular

abnor-malities

(such

as persistent

ductus

arteriosus)

have

a slightly

higher

cardiac

output

per

kilogram

of

body weight than term infants. The discrepancy

between

our

results

and

Alverson’s1’9

may

be due

to

the smaller number of patients in that study and

to the

technique

used

to estimate

aortic

diameter.

In

Alverson’s”9

studies,

systolic

aortic

internal

diameter

was

used

rather

than

the

late

diastolic

leading

edge

method

proposed

by

the

American

Society

of Echocardiography.8

In comparison

with

diastolic

internal

estimates,

systolic

internal

mea-surements lead to about a 5% overestimation of

aortic

diameter.

In contrast,

the

use

ofthe

leading

1200 ₁₂₀₀

0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0

BIRTHwEIGHT(kg) C. ‘ ‘ I 1 I I I I I II

Fig 1.

Relationship

between

birth

weight

and

pulsed

27 GESTATIONAL A:: (weeks) 42

Doppler

determinations

of cardiac

output

in neonates.

Fig 3.

Relationship

between

gestational

age and pulsed

Doppler determinations of cardiac output in neonates.

DISCUSSION

n= 121

y276.6- 10.4 Cx)

r-0.35

05 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0

BIRTHWEIGHT (kg)

Fig 2.

Relationship

between

birth

weight

and

pulsed

Doppler

determinations

of cardiac

output

expressed

per

kilogram of body weight in neonates.

mates were inclusive for this range. Cardiac output

also

increased

directly

with

increasing

gestational

age

(Fig

3) with

a correlation

coefficient

of .95

(P

<

.001).

Aortic

diameter

measurements

showed

a steady

increase

with

increasing

birth

weight

(Table),

with

a correlation

coefficient

of .89

(P

<

.001),

slope

=

0.11,

y-intercept

=

0.60 cm,

SD

= .067

cm,

and

a

(4)

edge method in systole leads to an increment of less

than 5%12

In our

study

we

measured

aortic

diam-eter with leading

edge

methodology

in early

diastole

instead of late diastole, because we found it a more

easily discernible point of measurement. It leads to values that are slightly lower than the end-systolic

leading edge dimension and slightly higher than the

end-diastolic leading edge dimension. This method

probably provides a more realistic reflection of the

aortic dimension from the opening of the aortic

valves to their closure. In consideration of the

van-able

expansion

of the

aortic

root

in systole8

and

the

inconsistences of recording techniques on the mea-sunement of the internal aortic diameter, we prefer the leading edge

method

in early

diastole.

Pulsed Doppler echocardiography for measuring

cardiac

output

has

been

tested

in animal

models7

and

is

being

increasingly

applied

to

older

chil-dren.13 With only a slight modification, we were

able

to

apply

this

method

in premature

and

term

neonates. To use this technique appropriately, one must

be aware

of its

limitations

and

potential

er-rors. Motion artifacts should be avoided, so the

patient should be studied during quiet sleep or be

adequately

restrained.

Angles

of

incidence

of the

Doppler

beam

should

not

exceed

15#{176}

to the

axis

of

the ascending aorta, as this will yield lower blood

flow

velocities

and

underestimate

cardiac

output

values.

Precise

measurement

of the

aortic

root

di-mension is critical because this measurement is

squared in the volumetric flow equation.

Further-more, the presence of a pneumothorax and/or a

pneumomediastinum prevents the passage of

ultra-sound and limits the use

of the

Doppler

technique

in these situations.

The results of our study compare favorably with

previous reports using invasive methods in healthy

neonates.’36 Emmanouilides et al’3 reported

mdi-cator dilution studies in 23 normal term neonates

(mean

birth

weight

3.27 kg)

at 6 to 34 hours

of age

and found a mean left ventricular output of 246 ±

95 mL/min/kg (830 ± 270 mL/min). Using similar

techniques, Gessner et al’4 reported cardiac output

values of 254 ± 53 mL/min/kg in 14 term neonates (mean birth weight 3.17 kg) at 0 to 2 hours

of age,

whereas Arcilla et al’5 measured mean values of 222

mL/min/kg in 47 term neonates (mean birth weight

3.63 kg) at

2#{189}to 54 hours of age. All of these results

are consistent with ours. Burnard et al’6 studied

left ventricular output by thermal dilution in a

group of 18 healthy term newborn infants (mean

birth weight 3.18 kg) aged 2 to 28 hours and found

cardiac

output

values

of

348

± 42 mL/min/kg.

Burnard’s’3’16 higher values can be explained by

cooling and the presence of significant left-to-right shunts at atrial and/or ductal levels. Noninvasive

cardiac

output

estimates

during

the

neonatal

period

using impedance cardiography provide inconsistent results in the lower range in comparison to the

Doppler

technique17”8

and

are

hampered

by

the

need

to use

a hematocnit-related

correction

factor.’7

Pulsed

Doppler

offers

a reliable

noninvasive

es-timate of cardiac output for clinical use in

new-borns. We have found the normal values and limits

presented

here

to be useful

in assessing

abnormal

cardiovascular

states

in the

newborn

nursery.

ACKNOWLEDGMENTS

The authors thank Jeanine King, MS, PA-C, and Greggory R. DeVore, MD, for technical assistance.

REFERENCES

1. Alverson DC, Eldridge M, Dillon T, et a!: Noninvasive pulsed Doppler determination of cardiac output in neonates and children. J Pediatr 1982;101:46-50

2. Sanders SP, Yeager 5, Williams RG: Measurement of sys-temic and pulmonary blood flow and Qp/Qs ratio using Doppler and two-dimensional echocardiography. Am J Car-diol 1983;51:952-956

3. Meyer RA, Kalavathy A, Korfhagen JC, et a!: Comparison of left to right shunt ratios determined by pulsed Doppler! 2D echo and Fick method. Circulation 1982;66(suppl 2):232 4. Lees MH: Cardiac output determination in the neonate. J

Pediatr 1983;102:709-711

5. Lubchenco LO, Hansman C, Boyd B: Intrauterine growth

in length and head circumference as estimated from live births at gestational ages from 24 to 42 weeks. Pediatrics

1966;37:403-408

6. Ballard JL, Novali KL, Driver M: A simplified score for

assessment of fetal maturation of newly born infants. J Pediatr 1979;95:769-774

7. Steingart RM, Meller J, Barovick J, et al: Pulsed Doppler

echocardiographic measurement of beat-to-beat changes in stroke volume in dogs. Circulation 1980;62:542-548

8. Sahn DJ, DeMaria A, Kisslo J, et al: Recommendations regarding quantitation in M-mode echocardiography:

Re-sults of a survey of echocardiographic measurements. Cir-culation 1978;58:1072-1083

9. Alverson DC, Eldridge MW, Johnson JD, et a!: Noninvasive measurement of cardiac output in healthy preterm and term newborn infants. Am J Perinatol 1984;1:148-151

10. Wallgren G, Hanson JS, Tabakin BS, et a!: Quantitative studies of the human neonatal circulation: V. Hemodynamic findings in premature infants with and without respiratory distress. Acta Paediatr Scand 1967;179(suppl):69-80

11. Greenfield JC Jr, Patel DJ: Relationship between pressure and diameter in the ascending aorta of man. Circ Res

1962;10:778-781

12. Reller MD, Meyer RA, Kaplan 5: Normal aortic root dimen-sions in premature infants. J Clin Ultrasound

1983;11:203-205

13. Emmanouilides GC, Moss AJ, Monset-Couchard M, et a!: Cardiac output in newborn infants. Biol Neonate 1970;15: 186-197

14. Gessner IH, Krovetz U, Benson RW, et a!: Hemodynamic adaptations in the newborn infant. Pediatrics

1965;36:752-762

15. Arcilla RA, Oh W, Waligren G, et al: Quantitative studies of the human neonatal circulation: II. Hemodynamic find-ings in early and late clamping of the umbilical cord. Acta Paediatr Scand 1967;179(suppl):23-42

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newborn infant. Gun Sci 1966;31:121-133

17. Costeloe K, Stocks J, Godfrey 5: Cardiac output in the neonatal period using impedance cardiography. Pediotr Res

1977;1 1:1171-1177

18. Freyschuss U, Noack G, Zetterstrom R: Serial measure-ments of thoracic impedance and cardiac output in healthy neonates after normal delivery and caesarean section. Acta Paediatr Scand 1979;68:357-362

PLINY THE YOUNGER

ON HIS WIFE’S

MISCARRIAGE

Pliny

the

Younger

(c. A.D.

61-112),

the

nephew

and

adoptive

son

of Pliny

the

Elder,

studied

under

Quintilian.

After

a brilliant

career

as a lawyer,

he was

praetor,

prefect

for the

treasury,

consul

and

governor

of Bithynia

under

Trajan.

Pliny

published

nine

books

of literary

letters

between

100 and

109 A.D.

One

of

his letters written to his third wife’s grandfather contained the following details

of her

miscarriage.’

I know how anxious you are for us to give you a great-grandchild, so you will be all

the more sorry to hear that your granddaughter has had a miscarriage. Being young and

inexperienced

she

did not realize she was pregnant, failed to take proper precautions,

and did several things which were better left undone. She has had a severe lesson, and

paid for her mistake by seriously endangering her life; so that although you must

inevitably feel it hard for your old age to be robbed of a descendent already on the way, you should thank the gods for sparing your granddaughter’s life even though they denied you the child for the present. They will surely grant us children later on, and we may take

hope

from

this

evidence

of her fertility,

though

the proof

has been

unfortunate.

I am giving you the same advice and encouragement as I use myself for your desire

for greatgrandchildren cannot be keener than mine for children. Their descent from

both of us should make their road to office easy; I can leave them a well-known name

and an established

ancestry

if only

they

may be born

and

turn

our present

grief to joy.

REFERENCE

Noted by T.E.C., Jr, MD

(6)

1985;76;829

Pediatrics

Frans J. Walther, Bijan Siassi, Naglaa A. Ramadan, Ananda K. Ananda and Paul Y. K. Wu

Clinical Use

Pulsed Doppler Determinations of Cardiac Output in Neonates: Normal Standards for

Services

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