Double-Blind Clinical Trial of Calf Lung Surfactant Extract for the Prevention of Hyaline Membrane Disease in Extremely Premature Infants

PEDIATRICS ◽  
1985 ◽  
Vol 76 (4) ◽  
pp. 585-592 ◽  
Author(s):  
Melinda S. Kwong ◽  
Edmund A. Egan ◽  
Robert H. Notter ◽  
Donald L. Shapiro
Keyword(s):  
Premature Infants ◽  
Controlled Trial ◽  
Lung Surfactant ◽  
Hyaline Membrane Disease ◽  
Treated Group ◽  
Efficiency Index ◽  
Lung Lavage ◽  
Exogenous Surfactant ◽  
Double Blind ◽  
Hyaline Membrane

A prospective, double-blind, controlled trial was conducted to determine whether instillation of an exogenous surfactant into the lungs before the first breath could prevent hyaline membrane disease. The surfactant is calf lung lipid extracted from saline lung lavage. Entry was limited to infants who were 24 to 28 weeks' gestation, who were born at Children's Hospital of Buffalo, and whose mothers had not received betamethasone for more than 24 hours before birth. Treated infants received 3 mL (90 mg) of calf lung surfactant extract instilled into their trachea before the first breath; control infants received 3 mL of normal saline. A prospective scoring system and respiratory support variables were used to compare the groups. At 48 hours of age, only two of 14 calf lung surfactant extract-treated infants (14%) had hyaline membrane disease compared with seven of 13 control infants (54%) (P = .033). Inspired oxygen, mean airway pressure, ventilator rate and ventilator efficiency index were also lower in the treated group during the first 48 hours of life (P < .01 to P < .001). Calf lung surfactant extract instillation at birth appears to be an effective material and method of preventing hyaline membrane disease in extremely premature infants.

Reduced Incidence of Hyaline Membrane Disease in Extremely Premature Infants Following Delay of Delivery in Mother With Preterm Labor: Use of Ritodrine and Betamethasone

PEDIATRICS ◽  
1986 ◽  
Vol 78 (5) ◽  
pp. 767-774
Author(s):  
Melinda S. Kwong ◽  
Edmund A. Egan
Keyword(s):  
Premature Infants ◽  
Controlled Trial ◽  
Lung Surfactant ◽  
Hyaline Membrane Disease ◽  
Treated Group ◽  
Efficiency Index ◽  
Premature Delivery ◽  
Aggressive Approach ◽  
Surfactant Production ◽  
Hyaline Membrane

Data from two groups of infants (24 to 28 weeks' gestational age) excluded from a controlled trial of the use of calf lung surfactant extract for the prevention of hyaline membrane disease are reported. The two groups were excluded from the trial because the mothers had received betamethasone for greater than 24 hours prior to delivery or because, on admission to the hospital, labor was too far advanced for proper informed consent to enter the trial. Attempts were made to delay delivery of threatened premature labor by the use of ritodrine in all mothers without evidence of infection, heavy vaginal bleeding, or severe preeclampsia and to induce surfactant production by maternal injection of betamethasone. A prospective scoring system and respiratory support variables were used to compare the groups. Infants born to mothers who successfully completed this regimen had a 28% incidence of hyaline membrane disease v a 68% incidence in infants in whose mothers it was unsuccessful due to inability to stop advanced labor (P = .001). Inspired oxygen, mean airway pressure, and ventilator rate were lower and the ventilator efficiency index was higher in the treated group during the first 48 hours of life. An aggressive approach to postpone premature delivery and to induce surfactant production by using tocolysis and a regimen of glucocorticoids reduces the incidence of hyaline membrane disease in very premature infants, 24 to 28 weeks' gestation.

Surfactant for Hyaline Membrane Disease

PEDIATRICS ◽  
1980 ◽  
Vol 66 (5) ◽  
pp. 795-798 ◽  
Author(s):  
Tetsuro Fujiwara ◽  
Forrest H. Adams
Keyword(s):  
Premature Infants ◽  
Lung Surfactant ◽  
Hyaline Membrane Disease ◽  
The Other ◽  
Synthetic Surfactant ◽  
Natural Surfactant ◽  
Hyaline Membrane ◽  
Dipalmitoyl Lecithin ◽  
Air Intake ◽  
Relative Deficiency

Since it has been demonstrated that hyaline membrane disease (HMD) is due to a relative deficiency of lung surfactant,1,2 one possible approach to the treatment or prevention of HMD in premature infants might be the introduction of surfactant into the lungs. Thus far, attempts at aerosolization of either synthetic surfactant (dipalmitoyl lecithin [DPL]) or natural surfactant into the lungs of patients or animals have failed to produce convincing benefits.3-5 On the other hand, direct instillation of a solution of natural surfactant into the trachea seems to produce striking results. Enhörning et al6 were the first to show that tracheal deposition of natural surfactant into premature rabbit fetuses before the first breath enhanced air intake and improved the pressure-volume relationships of the lungs; it also increased their survival time.7

Double-Blind, Randomized Trial of a Calf Lung Surfactant Extract Administered at Birth to Very Premature Infants for Prevention of Respiratory Distress Syndrome

PEDIATRICS ◽  
1985 ◽  
Vol 76 (4) ◽  
pp. 593-599 ◽  
Author(s):  
Donald L. Shapiro ◽  
Robert H. Notter ◽  
Frederick C. Morin ◽  
Karl S. Deluga ◽  
Leonard M. Golub ◽  
...  
Keyword(s):  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Premature Infants ◽  
Neonatal Intensive Care ◽  
Distress Syndrome ◽  
Lung Surfactant ◽  
Treated Group ◽  
Control Group ◽  
Double Blind ◽  
Severe Respiratory Distress

Organic solvent extraction of surfactant obtained by lavage of calf lungs yields a highly surfaceactive material. A double blind, randomized clinical trial to determine the effect of this material on respiratory distress syndrome in premature infants was initiated in the Neonatal Intensive Care Unit at the University of Rochester in December 1983. Infants 25 to 29 weeks gestational age were eligible for entry into the trial. At the time of this interim analysis 32 patients had been randomly selected and entered into the trial, 16 surfactant-treated patients and 16 in a control group who received only saline. At birth, intrapulmonary instillation of the calf lung surfactant extract dispersed in saline or saline alone occurred in the delivery room immediately after intubation and prior to ventilation; infants were then ventilated and treated as usual. At 6, 12, 24, 48, and 72 hours after birth, the severity of respiratory distress was categorized as either minimal, intermediate, or severe based on oxygen and mean airway pressure requirements. Differences observed at six hours after birth were of marginal significance, but at 12 and 24 hours the surfactant-treated group had significantly (P < .01) less severe respiratory distress compared with the control group. Differences between treated and control infants were not statistically significant at 48 and 72 hours after birth. In four surfactant-treated infants the severity of respiratory distress worsened between 24 and 48 hours after birth, suggesting that one dose of surfactant at birth may not be sufficient for some infants.

Randomized Controlled Trial of Exogenous Surfactant for the Treatment of Hyaline Membrane Disease

PEDIATRICS ◽  
1987 ◽  
Vol 79 (1) ◽  
pp. 31-37 ◽  
Author(s):  
Jonathan D. Gitlin ◽  
Roger F. Soll ◽  
Richard B. Parad ◽  
Jeffrey D. Horbar ◽  
Henry A. Feldman ◽  
...  
Keyword(s):  
Controlled Trial ◽  
Hyaline Membrane Disease ◽  
Respiratory Support ◽  
Exogenous Surfactant ◽  
Low Birth Weight Infants ◽  
Ventilator Support ◽  
Randomized Controlled ◽  
Acute Side Effects ◽  
Hyaline Membrane ◽  
Inspiratory Oxygen

We conducted a prospective, randomized, unblinded, controlled trial of exogenous bovine surfactant (surfactant TA) in premature infants requiring ventilator support for the treatment of severe hyaline membrane disease. Forty-one low birth weight infants with severe hyaline membrane disease were randomly assigned to saline or surfactant therapy and treated within eight hours of birth. Significant improvements in oxygenation (increased arterial/alveolar Po2) and respiratory support (decreased mean airway pressure) were seen in the group receiving surfactant within four hours after treatment. These improvements were maintained in the surfactant-treated infants, who also had fewer pneumothoraces and fewer number of days in environments of fractional inspiratory oxygen greater than 0.4 mm Hg. No problems were associated with administration of surfactant, and no acute side effects were detected. We conclude that exogenous surfactant, administered early in the course of severe hyaline membrane disease, is an effective therapy that can diminish the amount of respiratory support required during the first 48 hours of life.

DOUBLE-BLIND CONTROLLED TRIAL OF SINGLE-DOSE TREATMENT WITH BOVINE SURFACTANT IN SEVERE HYALINE MEMBRANE DISEASE

The Lancet ◽  
1987 ◽  
Vol 329 (8534) ◽  
pp. 651-656 ◽  
Author(s):  
TonseN.K Raju ◽  
Rama Bhat ◽  
KristineM Mcculloch ◽  
Haruo Maeta ◽  
Dharmapuri Vidyasagar ◽  
...  
Keyword(s):  
Single Dose ◽  
Controlled Trial ◽  
Hyaline Membrane Disease ◽  
Double Blind ◽  
Dose Treatment ◽  
Hyaline Membrane ◽  
Single Dose Treatment

STUDIES ON HYALINE MEMBRANE DISEASE

PEDIATRICS ◽  
1966 ◽  
Vol 38 (2) ◽  
pp. 244-253
Author(s):  
David H. Weintraub ◽  
Clara M. Ambrus ◽  
Julian L. Ambrus
Keyword(s):  
Prognostic Value ◽  
Prognostic Significance ◽  
Laboratory Data ◽  
Hyaline Membrane Disease ◽  
Final Diagnosis ◽  
Treated Group ◽  
X Rays ◽  
Additional Time ◽  
Double Blind ◽  
Initial Ph

In a group of 60 infants treated on a double-blind basis with placebo- or urokinase- activated human plasmin, clinical and laboratory data were analyzed in order to evaluate their diagnostic and prognostic value. Blood samples for laboratory studies were obtained at the time of final diagnosis and initiation of treatment, 4 hours later, and at additional time intervals if necessary. Respiratory rate and its changes during the first 4 hours appeared to be of little diagnostic or prognostic value. Chest x-rays alone did not appear to be useful in establishing diagnosis during the first 4 hours of life. In older infants, however, high diagnostic accuracy was obtained. Positive findings were generally dependable, but false negatives occurred in half of the cases. Improvement during serial x-ray examinations was a good prognostic sign but negative findings turning to positive ones were followed by survival in only one of two cases. Initial pH and pCO2 values varied widely. Changes in these parameters appeared to be of prognostic value in the placebo-treated infants but not in the urokinase-activated plasmin-treated group. In the latter, improvement in pH and pCO2, apparently due to increased respiratory gas exchange, was not sufficient to result in survival of the patient in the presence of additional pathology (e.g., pulmonary or intracranial hemorrhage, pneumonia). Generally, pH appeared to be a more sensitive predictive parameter than pCO2. Potassium levels and their changes during the first 4 hours were of no diagnostic or prognostic significance.

A Controlled Trial of Antepartum Glucocorticoid Treatment for Prevention of the Respiratory Distress Syndrome in Premature Infants, by G. C. Liggins, MB, PhD, FRCOG, and R. N. Howie, MB, MRACP, Pediatrics, 1972;50:515–525

PEDIATRICS ◽  
1998 ◽  
Vol 102 (Supplement_1) ◽  
pp. 250-252
Author(s):  
Mary Ellen Avery
Keyword(s):  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Distress Syndrome ◽  
Controlled Trial ◽  
Fetal Lung ◽  
Hyaline Membrane Disease ◽  
Treated Group ◽  
Premature Delivery ◽  
Glucocorticoid Treatment ◽  
Increased Risk

A controlled trial of betamethasone therapy was carried out in 282 mothers in whom premature delivery threatened or was planned before 37 weeks' gestation, in the hope of reducing the incidence of neonatal respiratory distress syndrome by accelerating functional maturation of the fetal lung. A total of 213 mothers were in spontaneous premature labor. When necessary, ethanol or salbutamol infusions were used to delay delivery while steroid or placebo therapy was given. Delay for at least 24 hours was achieved in 77% of the mothers. In these unplanned deliveries, early neonatal mortality was 3.2% in the treated group and 15.0% in the control subjects. There were no deaths with hyaline membrane disease or intraventricular cerebral hemorrhage in infants of mothers who had received betamethasone for at least 24 hours before delivery. The respiratory distress syndrome occurred less often in treated babies (9.0%) than in controls (25.8%), but the difference was confined to babies of <32 weeks' gestation who had been treated for at least 24 hours before delivery (11.8% of the treated babies compared with 69.6% of the control babies). There may be an increased risk of fetal death in pregnancies complicated by severe hypertension–edema–proteinuria syndromes and treated with betamethasone, but no other hazard of steroid therapy was noted. We conclude that this preliminary evidence justifies additional trials, but that additional work is needed before any new routine procedure is established.

STUDIES ON HYALINE MEMBRANE DISEASE

PEDIATRICS ◽  
1963 ◽  
Vol 32 (1) ◽  
pp. 10-24
Author(s):  
Clara M. Ambrus ◽  
David H. Weintraub ◽  
Donal Dunphy ◽  
John E. Dowd ◽  
John W. Pickren ◽  
...  
Keyword(s):  
Placebo Group ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Plasminogen Activator ◽  
Premature Infants ◽  
Distress Syndrome ◽  
Hyaline Membrane Disease ◽  
Blood Coagulation Factors ◽  
Plasminogen Activator Activity ◽  
Hyaline Membrane

In the serum of normal prematures and premature infants with respiratory distress syndrome, plasminogen was absent. In mature newborns plasminogen levels were low, as compared to adults. In the euglobulin fraction of plasma, plasminogen level was highest in mature newborns, lower in healthy prematures, and lowest in prematures with respiratory distress syndrome. Antiplasmin level was exceptionally high in about a fourth of the premature infants with or without respiratory distress syndrome. Plasminogen activator activity was found more often in the blood of infants with respiratory distress syndrome than in normal infants. This may be due to the liberation of tissue activators as a consequence of hypoxia. Because of the absence of the substrate (plasminogen), this activator level may have no significance. Tissue activator activity was found in the lungs of premature infants whether they died of hyaline membrane disease or from other causes. Forty-five infants with respiratory distress were treated in a therapeutic study. Twelve were treated in a preliminary series and 33 in a randomizd, double-blind investigation. Of the latter, 11 were treated with placebo, and 5 (45%) survived; 8 were treated with streptokinase activated human plasmin and 2 (25%) survived; 14 were treated with urokinase activated human plasmin and 12 (86%) survived. Among the infants who died, no definite hyaline membrane disease was found by histopathologic examination in two of the placebo group, one in the streptokinase-plasmin treated group, and the two who died in the urokinase-plasmin group. No significant side-effects of plasmin therapy were seen. Although considerable fibrinolytic and plasminogen-activator activity was generated in many treated patients, there was no significant fall in blood coagulation factors. Intracerebral hemorrhage, which appears to occur often in patients who die with hyaline membrane disease, was not more frequent in the plasmintreated group than in the placebo group.

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