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anterior cerebral arteries of newborn infants. A pulsatiity index (P1) is then calculated from the velocity tracings. The P1 value denotes the degree of resistance to cerebral blood flow: a low PT refers to significant advancing diastolic flow (low cerebral vascular resistance); a high PT refers to minimal advancing diastolic flow (high cerebral vascular re sistance).

Using this technique we studied eight infants with PDA who exhibited abnormal cerebral blood flow velocity patterns and the return to normal patterns following ductal closure.

METHODS ABSTRACT.Bloodflowpatternsin theanteriorcerebral

arteries were studied in eight preterm infants with patent

ductus arteriosus and left-to-right shunts. A noninvasive Doppler technique was used to obtain the blood flow patterns and to calculate a pulsatility index. Advancing diastolic blood flow was decreased in all eight infants, and two demonstrated retrograde anterior cerebral artery flow during diastole. Following ductal closure, the diastolic flow in the anterior cerebral arteries increased signif icantly, reaching levels seen in normal infants. These observations demonstrate that infants with patent ductus arteriosus and left-to-right shunts may have abnormal cerebral hemodynamics which return to normal following ductal closure. Pediatrics 69:778—781,1982;patent ductus arteriosus, cerebral blood flow.

Patient Population

The cerebral circulation has a low vascular re sistance which ensures the brain of continuous ad vancing blood flow throughout the cardiac cycle.'3 Studies ofthe flow velocity patterns ofthe carotid,4'5 vertebral,6'7 and anterior cerebral arteries8 all dem onstrate continuous antegrade flow even though velocity is not constant.

Blood flow velocity patterns in the aorta have also been studied.9'2 Normally aortic blood flow is predominantly antegrade with only minimal retro grade flow in early diastole. Significant diastolic retrograde aortic flow has been described in pa tients with aortic insufficiency'0 and in infants with patent ductus arteriosus (PDA).12―3These infants may thus have a decreased net blood flow down the aorta with resultant organ ischemia.'4

Bada et al8 have described a noninvasive Doppler

technique to assess the pulsatile flow within the

Received for publication August 10, 1981;accepted Nov 12, 1981. Reprint requests to (B.L.) Orlando Regional Medical Center, Division of Neonatology, 1414 S Kuhl Aye, Orlando, FL 32806. PEDIATRICS (ISSN 0031 4005). Copyright ©1982 by the

American Academy of Pediatrics.

After obtaining informed parental consent, eight preterm infants with left-to-right ductal shunts were studied. Infant characteristics are shown in Table 1. The mean gestational age was 29 ±2 (SD) weeks, mean birth weight, 1,063 ±326 (SD) gm, and mean age at diagnosis of the PDA, 4 days (range 2 to 10 days). The diagnosis of a left-to-right shunt across a PDA was established clinically by the presence of a characteristic murmur, hyperdyn amic precordium, and bounding pulses; and radio graphically by the findings of prominent pulmonary vasculature and cardiomegaly. In addition, left atrial to aortic root dimension ratios (LA/Ao) were assessed by echocardiography, and the degree of retrograde descending aortic flow expressed as a reverse to forward flow area ratio (R/F) was deter mined by continuous wave ultrasonography.'2

All eight infants were sick, seven required me chanical ventilation, and one infant (infant 1) re quired oxygen by hood. Blood pressure and arterial blood gas tension values were within normal limits at the time of the Doppler studies. These infants were not screened for intraventricular hemorrhage. Three infants had head ultrasound studies; infants

Abnormal Cerebral Hemodynamics in Preterm

Infants with Patent Ductus Arteriosus

Brian Lipman, MB, BCh (Rand), Gerald A. Serwer, MD, and Jane E. Brazy, MD

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TABLE1Characteristics*InfantBirthGesta. Infant Age atR/FtLA/AotTreatment/OutcomeNo.WeighttionalDiagno RatioRatio(gm)Age (wk)sis of PDA (days)11,1003020.051.10Fluid

restriction; PDA closed

day 1228202730.851.66Died day 631,0402920.761.81Ligated day 1241,0202830.511.88Ligated day 2651,13029100.401.48Ligated day 1968752930.741.73Ligated day 2271,7903360.051.06Fluid

restriction, PDA closed day

1987302640.741.79Ligated

day 11

* Abbreviations used are: PDA, patent ductus arteriosus; R/F, ratio of retrograde flow area to forward flow area in descending aorta; LA/Ao, left atrial to aortic root dimension ratio.

t Studies performed during ductal patency.

5 and 8 had moderate-sized intraventricular hem orrhages within 72 hours of birth and infant 6 had a normal study.

Doppler Technique

Pulsatile flow in the anterior cerebral arteries was assessed using a bidirectional Medasonics Versa tone D-9 Doppler flow meter and its analog two channel R-12 recorder. Advancing flow was dis played on the top channel and retrograde flow on the bottom channel. The bidirectional probe (P-94) was placed on the anterior fontanel and directed toward one of the anterior cerebral arteries as it travels from anterior to posterior along the medial aspect of the cerebral hemisphere. Doppler fre quency shift.s were recorded as velocity tracings, and the P1 was Calculated using the formula: P1 = S —¿D/S8 (Fig. 1). Values from the right and left sides did not differ significantly and a mean value for the two sides was CalcUlated.

Anterior cerebral artery velocity tracings were performed one to two times daily. Each infant had an average of four studies performed during the period ofshunting across the ductus and an average of 20 studie8 following ductal closure. Mean P1 values during ducts.! patency and following ductal closure were calculated for each infant, and statis tical analysis was performed using the paired t-test.

The normal range for the P1 in preterm infants

in our nursery was determined in a group of 40

infants who were stable in room air, required no respiratory support, and had normal blood pres sures and arterial blood gases. Their mean gesta tional age was 31.6 ±2 (SD) weeks; mean birth weight was 1,475 ±887 (SD) gm. The P1 values in these infants varied between 0.72 and 0.85 with mean of 0.79 ±0.04 (SD) and are similar to the

—¿@---s

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, +4 4

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ARTICLES 779

ADVANCING

Fig I . Velocitytracingfromanteriorcerebralartery.P1 = (S —¿D)/S; S is peak systolic velocity; D represents advancing flow velocity during diastole.

values found by Bada et al8 in normal term and preterm infants.

RESULTS

Six of the eight infants studied had large left-to right shunts as evidenced by increased R/F and LA/Ao ratios. One of these infants died and five infants had surgical ligation of their PDA. Infants

1 and 7 had normal R/F and LA/Ao ratios but had the typical clinical manifestations of a PDA which disappeared following fluid restriction.

The P1 values during ductal patency and follow ing ductal closure are shown in Table 2. The mean P1 value for infants during ductal patency was 0.90

± 0.06 (SD). Following ductal closure the P1 values

of all seven surviving infants were significantly lower, mean ±0.76 ±0.04 (SD) (P < 0.005), and were in the normal range. With ductal patency, infants 2 and 4 had P1 values as high as 1.0, during which time they demonstrated retrograde diastolic flow in the anterior cerebral arteries. Infant 2 died.

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TABLE 2.

Patency andPulsatility

Index (P1) Values During Ductal Following Ductal

Closure*Infant

No.Ductus Arteriosus Ductus Arteriosus

Open Closed1 2 3 4 5 6 7 80.90

±0.02 0.71 ±0.05

0.94 ±0.05j@

0.96 ±0.01 0.77 ±0.05

0.97 ±0.03t 0.81 ±0.09

0.84 ±0.01 0.82 ±0.07 0.88 ±0.02 0.74 ±0.05 0.89 ±0.06 0.74 ±0.06

0.80 ±0.04 0.74 ±0.04

Representative preligation and postligation tracings

for infant 4 are shown in Figs 2 and 3, respectively.

DISCUSSION

We have shown that infants with left-to-right ductal shunts have altered anterior cerebral artery blood flow patterns which return to normal follow ing ductal closure.

The etiology of these altered blood flow patterns is uncertain, but potential causes include: (1) cere bral vasoconstriction, (2) increased intracranial

0

* Values are means ± SD.

t Retrograde

flowduringdiastole

whenP1= 1.0.

0

Fig 2. Velocity tracing from anterior cerebral artery of infant 4 during ductal patency. Amplitude of D is zero and thus P1 = 1.0. Note retrograde flow occurs during diastole.

A0VANCING

RETROGRADE

Fig3. Velocitytracingfromanteriorcerebralarteryof infant 4 following ductal closure. P1 is now 0.82 (normal range), and there is no retrograde flow during diastole. pressure, and (3) ductal siphoning of cerebral blood flow (CBF). All three possibilities could result in a decreased diastolic blood flow. Cerebral vasocon striction appears an unlikely explanation as dis tressed preterm infants have been shown to have a loss of autoregulation of CBF with resultant vaso dilation.'5 Increased intracranial pressure was not clinically evident in these infants although this was not specifically measured. Neither vasoconstriction nor increased intracranial pressure explain the prompt return to normal of the flow patterns follow ing ductal ligation.

Ductal siphoning of CBF could explain the di minished diastolic flow in all eight infants, the retrograde flow in two infants, and the return to normal flow patterns following ductal closure. Si phoning of CBF has been described in adults with the subclavian steal syndrome,6'7―6 in patients with Blalock-Taussig shunts,'7 and in an infant with a preductal coarctation of the aorta.'8 Adults with the subclavian steal syndrome are often asymptomatic because of autoregulation of CBF and a generous collateral circulation at the circle of Willis; however, with arm exercise, siphoning of blood may lead to symptoms of cerebral ischemia.6―6

Because the distressed preterm infant often has impaired autoregulation of CBF, infants with pat ency of the ductus arteriosus and altered anterior cerebral artery flow patterns may be subject to cerebral ischemia. After ductal closure, the cerebral circulation may then be exposed to a surge in dia stolic blood flow and pressure, thus increasing the risk of intraventricular hemorrhage.

Not all infants with left-to-right shunts across a PDA exhibit these abnormal anterior cerebral ar tery flow patterns. However, the symptomatic in fant witb a large left-to-right shunt across a PDA

ADVANCING

I

I I I I I

RETROGRADE

I

I

I

I I

I

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I

@

@

@

@

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I I

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may have an altered cerebral hemodynamic pat 5. Strandness DE, Kennedy JW, Judge TP, et al: Transcuta neous directional flow detection: A preliminary report. Am Heart J 78:65, 1969

6. Keller HM, Meier WE, Kumpe DA: Noninvasive angiogra

phy for the diagnosis of vertebral artery disease using Dop pler ultrasound (vertebral artery Doppler). Stroke 7:364, 1976

7. Von Reutern G, Pourcelot L: Cardiac cycle-dependent alter

nating flow in vertebral arteries with subclavian artery ste noses. Stroke 9:229, 1978

8. Bada HS, Hajjar W, Chua C, et al: Noninvasive diagnosis of

neonatal asphyxia and intraventricular hemorrhage by Dop pler ultrasound. J Pediatr 95:775, 1979

9. Hunstman LL, Gams E, Johnson CC, et al: Transcutaneous

determination of aortic blood flow velocities in man. Am

Heart J 89:605, 1975

10. Boughner DR: Assessment of aortic insufficiency by trans

cutaneous Doppler ultrasound. Circulation 52:874, 1975

11. Benchiinol A, Stegall HF, Maroko PR, et al: Aortic flow velocity in man during cardiac arrythmias measured with

the Dopper catheter-flowmeter system. Am Heart J 78:649, 1969

12. Serwer GA, Armstrong BE, Anderson PAW: Noninvasive

detection of retrograde descending aortic flow in infants using continuous wave Doppler ultrasonography. J Pediatr 97:394, 1980

13. Cassell DE: The Ductus Arteriosus. Springfield, IL, Charles C Thomas, Publisher, 1973, pp 143-160

14. Kitterman JA: Effects of intestinal ischemia, in Moore TD

(ed): Necrotizing Enterocolitis in the Newborn Infant: Re

port of the 68th Ross Conference on Pediatric Research.

Columbus, OH, Ross Laboratories, 1975,pp 38-41

15. Lou HC, Lassen NA, Friis-Hansen B: Impaired autoregula

tion of cerebral blood flow in the distressed newborn. J

Pediatr 94:118, 1979

16. Patel A, Toole JF: Subclavian steal syndrome—reversal of

cephalic blood flow. Medicine 44:289, 1965

17. Serwer GA, Armstrong BE, Sterba RJ, et al: Alterations in carotid arterial velocity-time profile produced by the Blal ock-Taussig shunt. Circulation 63:1115, 1981

18. Daves, ML, Treger A: Vertebral grand larcency. Circulation

29:911, 1964

tern.

Cerebral hemodynamic abnormalities are often difficult to diagnose clinically in the sick preterm infant. The nomnvasive Doppler assessment of CBF patterns may be helpful in identifying those infants for whom a PDA represents a cerebral hemody namic hazard. Further studies are needed to define the mechanism by which a PDA may alter CBF patterns.

ACKNOWLEDGMENTS

Supported in part by a grant from the Heart Founda tion, and by National Institutes ofHealth grants HL11307 and HL20677.

REFERENCES

1. Keller HM, Meier WE, Yonekawa Y, et al: Noninvasive angiography for the diagnosis of carotid artery disease using Doppler ultrasound (carotid artery Doppler). Stroke 7:354,

1976

2. Planiol T, Pourcelot L: Doppler effect study of carotid circulation, in de Klieger M, White DN, McCready VR (eds):

Ultrasonics in Medicine: Proceedings ofthe Second World Congress, 1973. New York, American Elsevier Publishing

Co, 1974,pp 104—111.

3. Miyazaki M: Measurement of cerebral blood flow by ultra sonic Doppler technique: Hemodynamic correlation of inter

nal carotid artery and vertebral artery. Jpn Circ J 30:981,

1966

4. Keller HM, Meier WE, Anliker M, et al: Noninvasive mea

surement of velocity profiles and blood flow in the common carotid artery by pulsed Doppler ultrasound. Stroke 7:370,

1976

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1982;69;778

Pediatrics

Brian Lipman, Gerald A. Serwer and Jane E. Brazy

Abnormal Cerebral Hemodynamics in Preterm Infants with Patent Ductus Arteriosus

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1982;69;778

Pediatrics

Brian Lipman, Gerald A. Serwer and Jane E. Brazy

Abnormal Cerebral Hemodynamics in Preterm Infants with Patent Ductus Arteriosus

http://pediatrics.aappublications.org/content/69/6/778

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American Academy of Pediatrics. All rights reserved. Print ISSN: 1073-0397.

American Academy of Pediatrics, 345 Park Avenue, Itasca, Illinois, 60143. Copyright © 1982 by the been published continuously since 1948. Pediatrics is owned, published, and trademarked by the Pediatrics is the official journal of the American Academy of Pediatrics. A monthly publication, it has

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Figure

Fig 2.Velocity tracing from anterior cerebral artery ofand thus P1 = 1.0. Note retrogradeinfant 4 during ductal patency.Amplitudeof D is zeroflow occurs duringdiastole.

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