Frans J. Walther

Cardiac output in newborn infants with transient myocardial dysfunction

Decreased cardiac output is a common presumption in left ventricular myocardial dysfunction in neonates, but because of a lack of reliable noninvasive techniques, data on cardiac output are missing. We measured cardiac output by pulsed Doppler echocardiography in 22 newborn infants with left ventricular myocardial dysfunction diagnosed by M-mode echocardiography. Eleven neonates had severe perinatal asphyxia, seven had tachypnea, two hypoglycemia, and one septic shock; one had no symptoms. Right ventricular function was abnormal in 13 of the 22 infants. Hypotension was found in eight; cardiac output and stroke volume were low in 20. The abnormalities were more pronounced in infants with asphyxia. Six such infants were given dopamine (4 to 10 micrograms/kg/min). Within 1 hour, arterial blood pressure, cardiac output, stroke volume, and heart rate increased sharply, with normalization of the myocardial contractility; the other echocardiographic abnormalities normalized over 24 to 48 hours. Pulsed Doppler echocardiography is an advance in the detection and evaluation of therapy for left ventricular myocardial dysfunction in the neonate.

Prevalence and etiology of respiratory distress in infants of diabetic mothers: Predictive value of fetal lung maturation tests

Abstract The purpose of this study was to investigate the prevalence of respiratory distress syndrome attributable to surfactant deficiency in infants of diabetic mothers tested for fetal lung maturation. Three tests were assessed: (1) lecithin/sphingomyelin ratio, (2) phosphatidylglycerol concentration, and (3) optical density at 650 nm. From January 1987 through June 1989, 526 diabetic gestations were delivered within 5 days of fetal lung maturation testing. Surfactant-deficient respiratory distress syndrome was present in five infants (0.95%); all were n = 5), hypertrophic cardiomyopathy ( n = 4), pneumonia ( n = 2), polycythemia ( n = 1), and meconium aspiration syndrome ( n = 1). The use of standard maturity values of lecithin/sphingomyelin ratio ≥ 2.0, phosphatidylglycerol > 2% to 5%, and optical density at 650 nm ≥ 0.150 were evaluated. Each test had a 100% sensitivity in identifying surfactant-deficient respiratory distress syndrome and a 100% negative predictive value in identifying the absence of disease. All three tests had a low positive predictive value: 15% for lecithin/sphingomyelin ratio, 9% for phosphatidylglycerol, and 3% for optical density at 650 nm. We concluded that most cases of respiratory distress in the infants of diabetic mothers were unrelated to surfactant deficiency. The standard maturity values used in fetal lung maturation tests were valid in the diabetic gestation. The optical density at 650 nm was useful as a first-line test to predict the absence of surfactant-deficient respiratory distress syndrome.

Cerebral Blood Flow Velocity Regulation in Preterm Infants

Cerebrovascular autoregulation is the mechanism by which changes in cerebral blood flow are prevented during fluctuations in mean arterial blood pressure. Doppler ultrasound measurement of cerebral blood flow velocity provides a reliable indirect technique to estimate cerebral blood flow. In 48 stable preterm infants less than or equal to 32 weeks gestation, we studied the mean flow velocity in the pericallosal artery at 12, or at 12 and 72 h of age with two-dimensional/pulsed Doppler ultrasound and correlated the mean flow velocity with the simultaneously obtained mean arterial blood pressure values. Mean flow velocity was stable at a mean arterial blood pressure ranging from 31 to 40 mm Hg, but changed proportionally with mean arterial blood pressure values outside this narrow range. Multiple regression analysis showed that mean flow velocity was primarily determined by mean arterial blood pressure. These data suggest that in preterm infants regulation of cerebral blood flow velocity occurs only over a narrow range of mean arterial blood pressure values.

Cerebral blood flow velocity after surfactant instillation in preterm infants

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 infants 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.

Pulsed Doppler Measurement of Left Ventricular Output as Early Predictor of Symptomatic Patent Ductus arteriosus in Very Preterm Infants

High left ventricular output (LVO) values are associated with symptomatic left-to-right ductal shunting in preterm infants. However, LVO data prior to the occurrence of symptomatic patent ductus arteriosus (SPDA) are lacking. To determine whether serial measurements could predict a SPDA, we measured LVO from day 1 until day 10 with pulsed Doppler echocardiography in 25 preterm infants with birth weights of less than 1,250 g and hematocrits of more than 0.40. Eleven infants never developed patent ductus arteriosus symptoms and had LVO values within the normal range (190-310 ml/min/kg) with only minimal daily variations. The remaining 14 infants developed SPDA which required treatment with indomethacin, ductal ligation, or fluid restriction on days 2-5. From day 1 until day 5 their mean LVO values were significantly higher compared to the group without left-to-right ductal shunt and this increase was secondary to higher stroke volume values. An increase in LVO of more than 60 ml/min/kg consistently preceded SPDA by at least 24 h. Serial measurements of LVO using a single-pulsed Doppler approach can be used for early prediction of SPDA.

Ontogeny of Antioxidant Enzymes in the Fetal Lamb Lung

Pulmonary antioxidant enzyme ontogeny has been reported in species with a relatively short gestation such as hamsters, rats, rabbits, and guinea pigs. We examined the ontogeny of the antioxidant enzyme system together with the surfactant phospholipid disaturated phosphatidylcholine (DSPC) in fetal lamb lung (term is 148 days). Lung tissue from 36 fetuses with gestational ages ranging from 121 to 145 days were assayed for DSPC content and for the activities of three antioxidant enzymes: superoxide dismutase, catalase, and glutathione peroxidase. Between 121 and 145 days gestation superoxide dismutase activity increased from 25 +/- 4 to 139 +/- 18 IU/mg DNA, catalase activity from 164 +/- 23 to 483 +/- 48 IU/mg DNA, glutathione peroxidase activity from 301 +/- 33 to 447 +/- 53 IU/mg DNA, and DSPC content from 0.48 +/- 0.04 to 1.61 +/- 0.11 mg/mg DNA. During the final 15-20% of gestation in the fetal lamb antioxidant enzyme activity rises sharply in parallel with the development of the surfactant system.

Myocardial Dysfunction and Cerebral Blood Flow Velocity Following Birth Asphyxia

ABSTRACT. Birth asphyxia often leads to left ventricular myocardial dysfunction. To assess the effect of myocardial dysfunction on cerebral perfusion, we evaluated cardiac output and cerebral blood flow velocity in the anterior cerebral and internal carotid arteries in 20 asphyxiated term newborn infants during the first 4 days of life using 2‐dimensional/pulsed Doppler ultrasound. In 8 infants with myocardial dysfunction cardiac output was reduced on days 1 and 2 and within normal limits thereafter. In these infants changes in mean cerebral blood flow velocity and pulsatility index were passively related to changes in mean arterial pressure and cardiac output. In 12 infants without myocardial dysfunction a stable cerebral blood flow velocity pattern was found, which was unaffected by changes in mean arterial pressure. We conclude that infants presenting with a reduced cardiac output after deliveries associated with severe asphyxia may be at risk for additional ischemic or hemorrhagic cerebral damage because of lack of autoregulation.

Phospholipid and surfactant protein A concentrations in tracheal aspirates from infants requiring extracorporeal membrane oxygenation

To test the hypothesis that infants with severe respiratory failure and the need for extracorporeal membrane oxygenation (ECMO) are surfactant deficient, we measured the amount of surfactant phospholipids, disaturated phosphatidylcholine, surfactant protein A, and protein in tracheal aspirates from 22 infants, who received ECMO therapy for respiratory failure with meconium aspiration syndrome (n = 18) or pneumonia (n = 4). Tracheal suction material was obtained in a standardized way every 4 hours during the period of ECMO treatment and pooled for 24-hour periods. During ECMO, mean total phospholipid, disaturated phosphatidylcholine, and surfactant protein A values in tracheal aspirates increased and protein values decreased significantly, predominantly during the 72-hour period before infants were weaned from ECMO. Of the 22 infants, 14 had an increase in tracheal aspirate phospholipid values of more than 200% and were found to need a shorter period of ECMO support (p less than 0.005) and post-ECMO ventilatory support (p less than 0.025) than did the eight infants with stationary or only moderate increases in tracheal aspirate phospholipid values, three of whom had pneumonia. We conclude that infants with respiratory failure who require ECMO treatment often have surfactant deficiency. We speculate that surfactant treatment might decrease the need for or the duration of ECMO support.

Echocardiographic Measurements in Normal Preterm and Term Neonates

ABSTRACT. To the purpose of better defining normative data on intracardiac dimensions and systolic time intervals in very low birth weight infants, we collected M‐mode echocardiograms from 210 healthy preterm and term neonates with birth weights between 780 and 5350 g and gestational ages ranging from 26 to 43 weeks. Fifty‐nine neonates were less than 24 h, 62 were 25‐48 h, and 89 were 48‐144 h of age. Diastolic and systolic left ventricular dimensions increased gradually with advancing birth weight (r=+0.84 and 0.78). Left atrial and aortic root dimensions tended to show a parabolic relationship with birth weight, increments were reduced at higher birth weights (r=+0.92 and 0.85). The shortening fraction of the left ventricle (mean + SD 33.8 ± 4.9%) and the left atrial/aortic ratio (1.16 ± 0.10) were constant throughout all weight subgroups. Pre‐ejection periods and ejection times of both ventricles were reduced in preterm infants due to their higher heart rates, but left and right ventricular PEP/ ET ratios in preterm and term infants were comparable. Septal thickness in diastole and in systole tended to increase slowly with advancing birth weight, but correlation coefficients were low. This information is currently used as data base for a computer program to interpret M‐mode echocardiograms performed in our nursery.

Cardiac output changes secondary to theophylline therapy in preterm infants

The cardiovascular effects of theophylline were studied in 11 clinically stable preterm infants. Theophylline was given as aminophylline using a loading dose of 6.8 mg/kg and a maintenance dose of 2 mg/kg every 8 hours intravenously. Cardiac output, stroke volume, and heart rate were measured using a combination of pulsed Doppler ultrasound and M-mode echocardiography. Compared with day 0, an increase was found in both cardiac output (P