Multicenter study of surfactant (beractant) use in the treatment of term infants with severe respiratory failure,☆☆,,★★

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Abstract

Objective: The purpose of this study was to determine whether surfactant (beractant) administration to term newborns in respiratory failure and at risk for requiring extracorporeal membrane oxygenation (ECMO) treatment would significantly reduce the incidence of severe complications through 28 days of age and the need for ECMO. Study design: A multicenter (n = 44), randomized, double-blind, placebo-controlled trial was conducted. Infants weighing 2000 gm or more with gestational ages of 36 weeks or greater were stratified by diagnosis (meconium aspiration syndrome, sepsis, or idiopathic persistent pulmonary hypertension of the newborn) and oxygenation index (15 to 22, 23 to 30, 31 to 39) and then randomly assigned to receive four doses of beractant, 100 mg/kg (n = 167), or air placebo (n = 161) before ECMO treatment and four additional doses during ECMO, if ECMO was required. The incidence of untoward effects (including hemorrhagic, neurologic, pulmonary, renal, cardiovascular, infectious, metabolic, and technical complications) occurring before and after randomization and through 28 days of age or discharge were recorded. Results: The two treatment groups were comparable in baseline parameters, including birth weight, sex, gestational age, oxygenation index, and primary diagnosis. There was no difference in the incidence of severe complications. The need for ECMO therapy was significantly less in the surfactant group than in the placebo group (p = 0.038); this effect was greatest within the lowest oxygenation index stratum (15 to 22; p = 0.013). Conclusions: Use of surfactant, particularly in the early phase of respiratory failure, significantly decreases the need for ECMO in the treatment of term newborns with respiratory failure, without increasing the risk of complications. (J Pediatr 1998;132:40-7)

Section snippets

Patient Population

Two identical clinical studies were undertaken, and the combined results of the two studies are reported. Each center's institutional review board provided written approval of the protocol, and informed consent was obtained for each patient before randomization into the studies. The studies began on September 1, 1992, and the in-hospital phase was completed on October 23, 1995. Specific entry criteria included the following: (1) a gestational age of 36 completed weeks or older; (2) weight of

Demographic Data

During the study period, 1434 infants weighing at least 2000 gm, with gestational age of at least 36 weeks, not more than 120 hours of age, and with a diagnosis of either MAS, sepsis, or PPHN were screened for study entry at a total of 44 centers. Of these, 1104 (77%) did not meet entrance criteria; 872 infants (60%) were excluded from the study because they did not meet the requirement for 100% supplemental oxygen, were not within the required range for mean OI, or had previously received

Discussion

The results of this large multicenter study have shown that multiple doses of surfactant (beractant) in a population of term newborns with significant respiratory failure consistently and safely reduced the need for ECMO without increasing mortality rate or incidence of severe complications. The overall decrease in the need for ECMO demonstrated with the use of exogenous surfactant in this population was consistent from center to center in spite of variability in management. This study is the

Acknowledgements

The authors gratefully acknowledge the support and assistance of Billie Lou Short, MD. We also gratefully acknowledge the assistance of the Data Monitoring Committee: Reese Clark, MD, Alan Jobe, MD, PhD, P. Pearl O'Rourke, MD, Marilyn Escobedo, MD, and Thomas Fleming, PhD. We also thank James Elberfeld, Margaret Wyza, Karen Bennett, and Phillip Banks for their contributions to this project.

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    From the Division of Neonatology and Radiology, Department of Pediatrics, Children's National Medical Center, Washington, D.C.; Department of Pediatrics, The George Washington University School of Medicine and Health Sciences, Washington, D.C.; Ross Products Division, Abbott Laboratories; and Department of Pediatrics, University of Texas Health Science Center at San Antonio. *See Appendix.

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    Supported by the Ross Products Division of Abbott Laboratories.

    Reprint requests: Andrea Lotze, MD, Department of Neonatology, Loudun Hospital Center, Leesburg, VA 20176.

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