Haruo Maeta

ARTIFICIAL SURFACTANT THERAPY IN HYALINE-MEMBRANE DISEASE

Ten preterm infants severely ill with hyaline-membrane disease (HMD) were given artificial surfactant endotracheally. Oxygenation and alveolar-arterial oxygen gradients improved, the levels of inspired oxygen and peak respirator pressure could be reduced, and many of the radiological abnormalities resolved. Acidosis and systemic hypotension were also reversed. In nine infants a patent ductus arteriosus became evident after recovery from HMD, necessitating further assisted ventilation. Eight infants survived, including five of six with birthweight less than 1500 g; two died of unrelated causes. Postnatal tracheal instillation of artificial surfactant may prove a useful treatment for severe HMD.

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.

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)

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)

1552 COMPARISON OF TWO ANIMAL MODELS IN ARTIFICIAL SURFACTANT THERAPY FOR HYALINE MEMBRANE DISEASE (HMD)

Preterm baboon (B) and lambs (L) have been used as models for different surfactant studies. Varying responses have been recorded. We studied and compared the responses of these models to S-TA therapy. Animals delivered prematurely (B:76% and L:83% term) by C-section were used. All had HMD. S-TA 100 mg/kg was instilled into trachea at 2 hrs. of age. Controls received no S-TA. Sequential a/APO2 data are shown. Treated B had sustained improvement in a/APO2 up to 16 hrs. and mean airway pressure dropped from 14.5±1.1 to 10.2±0.5 cmH2O p<.001. In lambs improvement in a/APO2 was significant but transient lasting only 2-3 hrs, with deterioration by 4-5 hrs. Pressure vol. curves at autopsy showed significantly larger hysteresis in treated baboons than lambs. Two other treated baboons could be maintained alive for 36 hrs. We conclude: 1) Differences in response to S-TA therapy may be species related, 2) Baboon HMD model may be better for studies of long term effects of surfactant therapy than the lambs.

SURFACTANT TA (FUJIWARA) AND DRY SURFACTANT (MORLEY): EFFECTSON LUNG MECHANICS AND ALVEOLAR SIZE DISTRIBUTION IN PREMATURE RABBITS

We compared the efficacy of surfactant TA (Fujiwara) and the dry DPL+PG surfactant (DS, Morley) on pulmonary compliance (Cl), P-V curves and alveolar size distribution by texture analyzing systems (Leitz) in 4 groups of rabbits; 21 received 800 μg of TA suspended in saline (Gr.TA), 15 received DS surfactant (Gr.DS), 16 were premature controls (Gr.PC). All three groups were preterm delivered at 27 days gestation. Fourth group was mature controls (Gr.MC n=26). (Table: Mean ± S.E., *p <0.001).Premature controls had low volumes at P5 and P30 as compared to matures. Lung volumes reached mature levels in Gr.TA; in Gr.DS, improvement was less than in Gr.TA. Alveolar size distribution in Gr.TA was identical to mature controls, but marked non-homogeneous distribution of alveolar size was noted in Gr.DS. P-V curves and compliance differences were: Gr.TA showing mature pattern superior to Gr.DS. These results suggest that saline suspended S-TA improves pulmonary mechanics and alveolar histology to mature patterns to a greater extent than the dry surfactant of Morley et.al. (Abbr. in Table: P5 and P30=Pressure at 5 and 30 cm. H2O).

HEMODYNAMIC CHANGES FOLLOWING ARTIFICIAL SURFACTANT THERAPY: A CONTROLLED STUDY

Effects of exogenous surfactant (S-TA, Fujiwara) on hemodynamics and organ blood flow were studied in prematurely delivered baboons (76% term). Cardiac output (CO) and organ blood flow were measured before, 2 h and 7 h after surfactant using Sr85, Cr51 and Ce141, respectively. Colloid osmotic pressure (COP) was measured using osmometer (mm Hg). Diagnosis of PDA was confirmed by one shot angiography and at autopsy. Data from 3 control (A) and 2 S-TA treated (B) baboons are shown below.Organ blood is expressed as ml/min/gram (M±S.E). Ductal size was larger in surfactant treated baboons than in controls (3.5 mm vs 2.0 mm). This preliminary data suggest that (1) transient increase in lung blood flow seen after TA surfactant is secondary to large L to R shunt thru the PDA; (2) progressive increase in renal blood flow may be secondary to decrease in renal resistance; (3) colloid osmotic pressure increased in surfactant treated in comparision to control.

DOSE DEPENDANT EFFECTS OF SURFACTANT ON LUNG MECHANICS

Although exogenous surfactant replacement was proven to improve lung mechanics in clinical HMD (Fujiwara et.al. TA), optimal concentration and dose were not known. We studied the effect of different concentrations and quantity of TA in premature rabbits before first breath. Group A was treated with fixed lipid quantity, but variable TA concentration. Group B was treated with fixed concentration, but variable lipid quantity. We measured P-V curve (P-V) and lung-thorax compliance (CL) at 5 mg/ml to 40 mg/ml of concentration and 25 μg to 400 μg of quantity. Group A P-V curve data is given below. (Mean ± S.E.). In Group A, when lipid quantity was kept constant the variable concentration 10 mg/ml to 40 mg/ml of TA did not change the P-V curve and the CL. However when concentration of TA dropped to 5 mg/ml, the P-V curve and the CL changed adversely (p<0.02). Group B P-V curve and CL improved to maximum at 800 μg irrespective of concentrations. Further, the lipid quantity of 800 μg to 4000 μg had no further beneficial or adverse effect. We conclude 10 to 40 mg/ml of TA concentration,and lipid quanity of 800 μg to 4000 μg will have optimal effect on P-V curve and CL when instilled before the first breath.(*P5=5 cmH20 distending pr.).