Clinical and laboratory observations Cerebral blood flow velocity after surfactant instillation in preterm infants M a r g o t v a n d e Bor, MD, PhD, Ellen J. M a , MD, a n d Frans J. W a l t h e r , MD, PhD From the Division of Neonatology, Department of Pediatrics, University of Southern California School of Medicine, Los Angeles County and University of Southern California Medical Center, Los Angeles

Various clinical trials have shown that surfactant replacement therapy improves pulmonary function in preterm infants with respiratory distress syndrome. However, this is not accompanied by a concomitant decrease in the incidence and severity of intracranial hemorrhages, t Using Doppler ultrasound measurement of blood flow velocity in the pericallosal artery, z we attempted to determine whether endotracheal surfactant instillation affects cerebral hemodynamics and, if so, whether it predisposes preterm infants to the occurrence of intracranial hemorrhage. METHODS The study population consisted of 25 preterm infants without congenital malformations and with birth weights of more than 1100 gm who were born at the Los Angeles County and University of Southern California Medical Center. The study was approved by the bioethics committee of the hospital. Written informed parental consent was obtained before each infant's enrollment in the study. Fifteen consecutively admitted infants with severe respiratory distress syndrome, defined by an arterial/alveolar ratio of 0.22 or less during support by mechanical ventilation, received a synthetic lung surfactant (Exosurf Pediatric) by intratracheal instillation when they were between 2 and 24 hours of age. Infants whose mothers had amuionitis

Dr. Van de Bor was the recipient of a Fulbright research scholarship. Submitted for publication June 12, 1990; accepted Aug. 30, 1990. Reprint requests: Frans J. Walther, MD, PhD, Department of Pediatrics, King/Drew Medical Center and University of California at Los AngelesSchool of Medicine, 12021 S. Wilmington Ave.,Los Angeles, CA 90059. 9/24/25100

and infants with clinical evidence of infections were excluded from the study. After endotracheal suctioning, surfactant was instilled in two doses of 2.5 ml/kg each, one dose for each lung. The instillation procedure took approximately 4 minutes. Ten preterm infants, matched for birth weight and gestational age, who were supported by mechanical ventilation for respiratory distress syndrome but not treated with surfactant, served as control subjects. These infants were studied before and after routine endotracheal suctioning. Blood flow velocity waveforms in the pericallosal artery were obtained by two-dimensional pulsed Doppler ultrasonography with the anterior fontanel serving as an acoustic window. The artery was insonated at its curve around the FIO2 Pco 2 Po2

Fractional inspired oxygen Partial pressure of carbon dioxide Partial pressure of oxygen

corpus callosum with a 5 MHz Doppler crystal and a 7.5 MHz imaging system (Ultramark 8, Advanced Technology Laboratories, Bothell, Wash.) at an angle of insonation of less than 10 degrees. The sample volume of the Doppler system was set at 1.5 mm, and a 100 Hz high-pass filter was used to reduce noise from the pulsating arterial wall. The Doppler signals were subjected to real-time spectral analysis. Peak systolic, end-diastolic, and mean flow velocities in centimeters per second were determined from five sequential cardiac cycles of optimal quality and averaged. 3 During the examination the infants were in a supine position. Cerebral blood flow velocity was measured before and 5, 10, 15, 20, 30, and 40 minutes after surfactant instillation or routine suctioning. Simultaneously with the Doppler measurements, mean arterial blood pressure from an



Clinical and laboratory observations

"J-P< 0.05 * P < 0,01 * * P < 0.001

The Journal of Pediatrics February 1991

9 SURFACTANT (n=15) o CONTROL (n=10)

T a b l e . Perinatal data (mean _+SD or range) in the

surfactant-treated and control infants


Gestational age (wk) Birth weight (gm) Apgar score 1' (median) Apgar score s' (median) pH at admission Mode of delivery Vaginal Cesarean section Gender (M/F) Mean airway pressure before instillation/ suetioning (cm H20)




50f 40


Surfactant (n ~ 15)

Control (n = 10)

29.9 _+ 1.0 1401 +_ 263 4.5 (2-8) 7 (5-9) 7.31 _+ 0.04

29.0 • 1.6 1332 • 48 5 (5-6) 7 (7-8) 7.33 _+ 0.04

6 9 9/6 7.46 _+ 3.10

4 6 5/5 7.01 +_ 0.01

The p values were not significant.


100 90

80 70 60 50

" i qL5 I 5

rate, Po2 or Pcoz, and cerebral blood flow velocity with multiple regression analysis.




50f 40


HR(bpm) 160 f 150 140 ~


pre I















Figure. Mean flow velocity (MFV), mean arterial blood pressure

(MABP), blood gas values (Po2 and Pcos), and heart rate (HR) before and after surfactant instillation (e) or endotracheal suctioning (o). indwelling umbilical artery catheter, heart rate, ventilator settings, and transcutaneous P02 and Pc02 data were obtained. The data are expressed as means _+ SD. Student t and chi-square tests were used to determine differences in perinatal data, cerebral blood flow velocity, mean arterial blood pressure, and transcutaneous P02 and Pc02 between the" treated and the control infants. Differences within the treated group were determined with analysis of variance, and the association of mean arterial blood pressure, heart

The infants treated with surfactant and the control infants had similar gestational ages, birth weights, Apgar scores, pH at admission, and mean airway pressures (Table). Mean flow velocity in the pericallosal artery increased by 35% after the instillation of surfactant and returned gradually to baseline values within 30 minutes (p

Cerebral blood flow velocity after surfactant instillation in preterm infants.

Clinical and laboratory observations Cerebral blood flow velocity after surfactant instillation in preterm infants M a r g o t v a n d e Bor, MD, PhD,...
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