A Multicenter Randomized, Placebo-Controlled Trial of Surfactant Therapy for Respiratory Distress Syndrome

• Published in: The New England journal of medicine Vol. 320; no. 15; pp. 959 - 965
• Main Authors: Hobar, Jeffrey D, Soll, Roger F, Sutherland, James M, Kotagal, Uma, Philip, Alistair G.S, Kessler, Dale L, Little, George A, Edwards, William H, Vidyasagar, Dharmapuri, Raju, Tonse N.K, Jobe, Alan H, Ikegami, Machiko, Mullett, Martha D, Myerberg, David Z, McAuliffe, Timothy L, Lucey, Jerold F
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Boston, MA Massachusetts Medical Society 13.04.1989
• Subjects: Babies; Biological and medical sciences; Birth weight; Bronchopulmonary Dysplasia - complications; Cerebral Hemorrhage - complications; Clinical Trials as Topic; Ductus Arteriosus, Patent - complications; Evidence-based medicine; Female; Humans; Infant, Newborn; Male; Medical sciences; Multicenter Studies as Topic; Oxygen - analysis; Pediatrics; Pharmacology. Drug treatments; Phospholipids; Pneumothorax - etiology; Pulmonary Surfactants - administration & dosage; Pulmonary Surfactants - therapeutic use; Random Allocation; Respiratory distress syndrome; Respiratory Distress Syndrome, Newborn - drug therapy; Respiratory Distress Syndrome, Newborn - mortality; Respiratory Distress Syndrome, Newborn - physiopathology; Respiratory system; Respiratory therapy; Surfactants; Ventilators; Human; Therapeutic efficiency; PaO2; Chemotherapy; Newborn; Treatment; Respiratory disease; Multicenter study; Single dose; Respiratory distress; Controlled therapeutic trial; Surfactant
• ISSN: 0028-4793; 1533-4406
• DOI: 10.1056/NEJM198904133201502

We carried out a multicenter randomized, placebo-controlled trial to evaluate the efficacy and safety of surfactant in the treatment of respiratory distress syndrome. The study population was made up of newborn infants weighing 750 to 1750 g who were receiving assisted ventilation with 40 percent or more oxygen. The eligible infants received a single dose of either surfactant (100 mg of phospholipid per kilogram of body weight [4 ml per kilogram]) or an air placebo (4 ml per kilogram), administered into the trachea within eight hours of birth by an investigator not involved in the clinical care of the infant. When compared with the infants who received the placebo(n = 81), the infants who were treated with surfactant (n = 78) had a 0.12 greater average increase in the ratio of arterial to alveolar oxygen tension (P<0.0001), a 0.20 greater average decrease in the fractional inspiratory oxygen concentration (P<0.0001), and a 0.26-kPa greater average decrease in the mean airway pressure (P<0.0001) during the 72 hours after treatment. Pneumothorax was less frequent among the infants treated with surfactant than in the control group (13 percent vs. 37 percent; P = 0.0005). There were no statistically significant differences between the groups in the proportion of infants in each of five ordered clinical-status categories on day 7 (P = 0.08) or day 28 (P = 0.75) after treatment. There were also no significant differences between the groups in the frequency of bronchopulmonary dysplasia, patent ductus arteriosus, necrotizing enterocolitis, or periventricular–intraventricular hemorrhage. In each group, 17 percent of the infants died by day 28. We conclude that treatment with the single-dose surfactant regimen used in this study reduces the severity of respiratory distress during the 72 hours after treatment and decreases the frequency of pneumothorax, but that it does not significantly improve clinical status later in the neonatal period and does not reduce neonatal mortality. Further study of different surfactant regimens and patient-selection criteria will be required to determine whether this initial improvement can be translated into reductions in mortality or serious morbidity. (N Engl J Med 1989; 320:959–65.) SINCE 1980, when Fujiwara and coworkers 1 first described improvements in oxygenation and ventilation after infants with established respiratory distress syndrome were treated with surfactant, the usefulness of exogenous surfactant from human or other animal sources to modify the course of respiratory disease in infants with respiratory distress syndrome or at risk for this syndrome has been confirmed in 13 randomized, controlled trials. 2 3 4 5 6 7 8 9 10 11 12 13 14 These trials have varied in terms of their patient-selection criteria, the surfactant preparations used, and the timing and dosage of surfactant administration. Despite the differences in study design, the intratracheal administration of surfactant resulted in improved blood gas . . .