Senji Shimada

Effects of patent ductus arteriosus on left ventricular output and organ blood flows in preterm infants with respiratory distress syndrome treated with surfactant

Thirty preterm infants (birth weight < 1500 gm) treated with Surfactant TA for the respiratory distress syndrome, who had no complicating clinical problems other than ductal patency, were studied by serial Doppler flow examinations to determine the effects of early left-to-right shunt through the patent ductus arteriosus on the left ventricular output and organ blood flows. Doppler flow variables in 15 infants with a hemodynamically significant patent ductus arteriosus (hsPDA) were compared with those in 15 subjects without hsPDA matched for age, body weight, and gestational age. Infants with hsPDA had significantly higher left ventricular output and significantly lower blood flow volume in the abdominal aorta, and lower temporal mean blood flow velocities, with concomitant increases in the relative vascular resistance in the celiac artery, superior mesenteric artery, and renal artery. Pulsatility indexes of these vessels and the anterior cerebral artery were significantly higher in the hsPDA group, but the temporal mean blood flow velocities in the anterior cerebral artery and its vascular resistance were not significantly different between the two groups. After closure of the patent ductus arterious was achieved with mefenamic acid therapy, alterations in Doppler flow variables in the hsPDA group reverted to the levels seen in the group without hsPDA. These results suggest that despite large left-to-right ductal shunting, the heart of the preterm infant is capable of mounting a compensatory increase of cardiac output sufficient to maintain unchanged cerebral blood flow, but is unable to maintain postductal organ blood flows because of decreased perfusion pressure (ductal steal) and localized increase in vascular resistance.

Cardiocirculatory effects of patent ductus arteriosus in extremely low-birth-weight infants with respiratory distress syndrome

Background : Cardiocirculatory effects of hemodynamically significant patent ductus arteriosus (hsPDA) have not been systematically studied in extremely low‐birth‐weight (ELBW) infants with respiratory distress syndrome (RDS). The objective of the present study was to evaluate the effects of hsPDA on the left ventricular output (LVO) and organ blood flows in ELBW infants with RDS.

A prospective, randomized trial of early versus late administration of a single dose of surfactant-TA

Thirty-two neonates weighing 500-1500 g with documented surfactant deficiency and without evidence of severe birth asphyxia, infection, prolonged rupture of membranes greater than or equal to 72 h, or oligohydramnios were randomly assigned to receive a single intratracheal dose of surfactant-TA (100 mg/kg) either within 30 min of birth (n = 16, early group) or at 6 h of age (n = 16, late group). By 6 h of age, all neonates of the late group had moderate/severe RDS, while none of the neonates of the early group had either clinical or radiological respiratory distress syndrome. The incidence of bronchopulmonary dysplasia was significantly lower in survivors of the early group than those of the late group (1/15 versus 7/14, a 43% reduction with a 95% confidence interval of 14-72%, P = 0.025). These beneficial effects of early surfactant treatment remained after controlling for the various confounding factors in the logistic models.

Treatment of patent ductus arteriosus after exogenous surfactant in baboons with hyaline membrane disease.

ABSTRACT: The effect of early treatment of patent ductus arteriosus (PDA) on the acute course of hyaline membrane disease was tested in a primate model, after intratracheal administration of 100 mg/kg exogenous bovine surfactant phospholipids at mean ages between 2.3-2.4 h. Twentytwo premature baboons were divided into four groups: seven animals were controls (group A); five were treated with surfactant but PDA was not intervened (group B); in five surfactant treatment was followed by three doses of 0.2 mg/kg intravenous indomethacin beginning at a mean age of 5.5 h (group C); and in five surfactant treatment was followed by a surgical ligation of PDA between 5-5.5 h of age. After surfactant instillation in groups B, C, and D, a prompt and sustained improvement was noted in a/APO2, mean airway pressure, ventilator efficiency index and pulmonary compliance. However, no consistent differences were found in the respiratory variables within the surfactant treated groups during the 72-h experiment: the respiratory course in the animals treated for PDA (groups C and D) was generally similar to the animals in which PDA was not treated (group B). In animals treated with surfactant and indomethacin (group C) the mean aortic blood pressure was maintained more optimally as compared to the other three groups. These findings suggest that although a significant early ductal shunting does occur after exogenous surfactant therapy in this animal model, the expected pulmonary deterioration does not occur, and an early abrupt interruption of PDA does not seem to provide additional advantage to the immediate course of hyaline membrane disease.

Surfactant Replacement Therapy in Premature Babies with Respiratory Distress Syndrome: Factors Affecting the Response to Surfactant and Comparison of Outcome from 1982–86 and 1987–91

The impact of surfactant therapy on chronic lung disease remains uncertain. During the past decade (1982–91), over 300 babies with respiratory distress syndrome (RDS) weighing 501–2,500 g at birth were consecutively treated with surfactant‐TA at our neonatal intensive care unit. Data on 95 RDS babies treated in the first 5 year period (Period 1, 1982–86) were compared with those on 158 RDS babies treated in the second 5 year period (Period 2, 1987–91). Overall respiratory improvement was better in Period 2 than in Period 1. In Period 2, surfactant therapy converted 98% of the babies with moderate/severe RDS to those with ‘near normal’ lung by 72 hr post‐treatment. In Period 2, 95% of the surfactant‐treated babies weighing 501–1,750 g at birth survived, 97% of which required no supplemental oxygen at 40 weeks corrected gestational age. Increased survival rate in the surfactant‐treated babies during the past decade has not been followed by a parallel increase in chronic lung disease. The severity of the initial pulmonary disease per se was not the significant risk factor for chronic lung disease. Several other variables affecting the response to surfactant therapy and outcome have been identified by stepwise logistic regression analysis and include factors related to perinatal events such as birth asphyxia and infection, and other complications of prematurity.

Effect of exogenous surfactant on the development of bronchopulmonary dysplasia in a baboon hyaline membrane disease model

To test the effect of exogenous surfactant on the evolution of histopathologic changes of bronchopulmonary dysplasia (BPD), we conducted a study in a premature baboon hyaline membrane disease model. One hundred mg/kg bovine surfactant sonicated in saline or 3 ml/kg saline placebo was instilled via the trachea at about 10 min of age. The clinical status and physiologic changes were monitored for 9 days, and pulmonary histopathology was evaluated after death. Compared to the control, the surfactant-treated animals showed a significant improvement in arterial/alveolar oxygen ratio and pulmonary compliance, facilitating rapid weaning from assisted ventilation. Lung histology revealed that pulmonary parenchyma expanded 70% to 95% without features of early BPD. Dysplastic maturation, air trapping, or cellular atypia was not seen. In contrast, lung histology in the control group revealed alveolar expansion < 50%, basal cell hyperplasia in the bronchial and bronchiolar epithelium, dysplastk maturation with cellular atypia, extensive epithelial erosion, and type II cell hyperplasia, all features of early BPD. The results of this study suggest that in the premature baboon model, exogenous surfactant therapy improves pulmonary functional abnormalities and lessens the histologic features of BPD, perhaps because of rapid weaning and reduced barotrauma. (Crit Care Med 1990; 18:403)

Surfactant proteins and stable microbubbles in tracheal aspirates of infants with respiratory distress syndrome: relation to the degree of respiratory failure and response to exogenous surfactant.

Abstract Surfactant proteins (SP-A and SP-BC), albumin (ALB), and stable microbubble (SM) count were measured in tracheal aspirates from infants with respiratory distress syndrome (RDS) receiving single-dose Surfactant-TA (surfactant group, n = 32) or no surfactant (control group, n = 12), and those without RDS (non-RDS group, n = 8) to determine biochemical and biophysical status of surfactant in the course of RDS after surfactant replacement. Surfactant therapy resulted in immediate and sustained elevations of SP-BC/ALB and SM count with a rapid fall in ventilatory index to levels measured in the non-RDS group, whereas these indices improved slowly in the control group. The SP-A/ALB was initially low in both RDS groups and increased to levels measured in the non-RDS group by age 48 h. Multiple regression analysis showed that SP-BC/ALB, postnatal age, SM count, SM count/SP-A plus SP-BC, and surfactant therapy were independently associated with the severity of RDS as assessed by ventilatory index (r = 0.75, P < 0.0001; number of samples = 256). Infants with a relapse response to surfactant (n = 9) had levels of SP-A/ALB and SP-BC/ALB similar to those measured in the sustained group (n = 23), but had significantly lower SM count and SM count/SP-A plus SP-BC between 24 and 96 h of age. Conclusion Surfactant therapy normalizes the sur factant and respiratory status of infants with RDS. Surfactant dysfunction rather than depletion may explain the relapse response seen in some surfactant recipients.

EXOGENOUS SURFACTANT THERAPY IN INFANTS WITH RDS: COMPARISON OF EARLY VS LATE TREATMENT

We report successful treatment of RDS with exogenous surfactant (TA). We studied the clinical course of three groups of infants with RDS. Control Grp. (C,n10) did not receive TA, early Grp. (E,n 10) received TA at a [xmacr ] age of 3½ hrs. Late Grp. (L,n10) received surfactant at [xmacr ]=8½ hrs. of age. TA surfactant dispersed in saline was given via endotracheal tube. Results of sequential MAP and a/APO2 are shown below. There were no differences in B.Wt. and GA between the Grps. Before treatment MAP and a/APO2 were the same in all Grps. Following therapy, MAP dropped significantly both in E & L Grps. (p<.01) by 1 hr. It decreased steadily in Grp. E. The differences between Grps. E and L were also significant (p<.01). Similarly, a/APO2 improved significantly (p<.01) in both Grps. E and L 1 hr. following treatment. Chest x-rays cleared rapidly in E & L Grps., but not in Grp. C. However, treated Grp. had high incidence of silent PDA. There were no deaths in any group. We conclude that: a) TA treatment rapidly improves the course of RDS; b) E treatment rapidly decreases MAP than Grp. L; and c) both E & L treatment are equally beneficial.

Chest radiographic course after exogenous surfactant therapy in baboons with respiratory distress syndrome

Exogenous surfactant materials have been used under a variety of treatment protocols in cases of neonatal respiratory distress syndrome (RDS). To evaluate the differences in radiologic changes that follow either an early or late therapy with exogenous bovine surfactant, we reviewed 189 serially obtained chest radiographs from 48 premature baboons with RDS studied under different treatment regimen. Twenty-six animals were controls (100 chest films), and 22 received 100 mg/kg bovine surfactant instilled via the trachea in three study protocols (89 chest films). Surfactant was given within 10 min of birth in one group and at 2 h of age in the other. In 25/26 controls, radiologic evidence of severe RDS was seen by 2 h of age; these changes persisted in 15 animals at 24 h. By contrast, a rapid clearing of radiologic features of RDS was seen following surfactant instillation in all 22 (100%) animals within 4 h, but one (4.5%) of these 22 deteriorated at 9 h of age. Pulmonary interstitial emphysema (PIE) was seen in 9/26 (34.6%) and pneumothorax in 5/26 (19.2%) control animals, while 1/22 (4.5%) surfactant-treated animals developed PIE, and none had pneumothorax. The presence of a shunt via the patent ductus arteriosus did not affect radiographic findings in 20 animals studied by contrast injection. Therapy for patent ductus arteriosus (PDA) also had no substantial influence on the radiographic findings, or with regard to the pulmonary course. Radiographic clearing of RDS occurred approximately 18 to 20 h prior to the improvement in pulmonary compliance.(ABSTRACT TRUNCATED AT 250 WORDS)