James J Cummings1, Erick Gerday2, Stephen Minton2, Anup Katheria3, George Albert4, Jaime Flores-Torres5, Mobolaji Famuyide6, Andrea Lampland7, Scott Guthrie8, Devon Kuehn9, Jörn-Hendrik Weitkamp10, Prem Fort11, Elie G Abu Jawdeh12, Rita M Ryan13, Gregory C Martin14, Jonathan R Swanson15, Neil Mulrooney16, Fabien Eyal17, Dale Gerstmann18, Praveen Kumar19, Greg E Wilding20, Edmund A Egan21. 1. Albany Medical Center, Albany, New York; cummings.AMBI@gmail.com. 2. Utah Valley Regional Medical Center, Provo, Utah. 3. Sharp Mary Birch Hospital for Women and Newborns, San Diego, California. 4. Sisters of Charity Hospital, Buffalo, New York. 5. Tampa General Hospital, Tampa, Florida. 6. Department of Pediatrics, University of Mississippi, Oxford, Mississippi. 7. Children's Minnesota St. Paul Hospital, St. Paul, Minnesota. 8. Jackson-Madison County General Hospital, Jackson, Tennessee. 9. East Carolina University and Vidant Medical Center, Greenville, North Carolina. 10. Vanderbilt University Medical Center, Nashville, Tennessee. 11. Johns Hopkins All Children's Hospital, St. Petersburg, Florida. 12. University of Kentucky Children's Hospital, Lexington, Kentucky. 13. Department of Pediatrics, Medical University of South Carolina, Charleston, South Carolina. 14. Phoenix Children's Hospital, Phoenix, Arizona. 15. University of Virginia Children's Hospital, Charlottesville, Virginia. 16. Children's Minneapolis Hospital, Minneapolis, Minnesota. 17. University of South Alabama Children's and Women's Hospital, Mobile, Alabama. 18. Timpanogos Regional Hospital, Orem, Utah. 19. Order of St. Francis Children's Hospital of Illinois, Peoria, Illinois. 20. Department of Biostatistics, University at Buffalo, Buffalo, New York; and. 21. ONY Biotech, Amherst, New York.
Abstract
BACKGROUND: Exogenous surfactants to treat respiratory distress syndrome (RDS) are approved for tracheal instillation only; this requires intubation, often followed by positive pressure ventilation to promote distribution. Aerosol delivery offers a safer alternative, but clinical studies have had mixed results. We hypothesized that efficient aerosolization of a surfactant with low viscosity, early in the course of RDS, could reduce the need for intubation and instillation of liquid surfactant. METHODS: A prospective, multicenter, randomized, unblinded comparison trial of aerosolized calfactant (Infasurf) in newborns with signs of RDS that required noninvasive respiratory support. Calfactant was aerosolized by using a Solarys nebulizer modified with a pacifier adapter; 6 mL/kg (210 mg phospholipid/kg body weight) were delivered directly into the mouth. Infants in the aerosol group received up to 3 treatments, at least 4 hours apart. Infants in the control group received usual care, determined by providers. Infants were intubated and given instilled surfactant for persistent or worsening respiratory distress, at their providers' discretion. RESULTS: Among 22 NICUs, 457 infants were enrolled; gestation 23 to 41 (median 33) weeks and birth weight 595 to 4802 (median 1960) grams. In total, 230 infants were randomly assigned to aerosol; 225 received 334 treatments, starting at a median of 5 hours. The rates of intubation for surfactant instillation were 26% in the aerosol group and 50% in the usual care group (P < .0001). Respiratory outcomes up to 28 days of age were no different. CONCLUSIONS: In newborns with early, mild to moderate respiratory distress, aerosolized calfactant at a dose of 210 mg phospholipid/kg body weight reduced intubation and surfactant instillation by nearly one-half.
BACKGROUND: Exogenous surfactants to treat respiratory distress syndrome (RDS) are approved for tracheal instillation only; this requires intubation, often followed by positive pressure ventilation to promote distribution. Aerosol delivery offers a safer alternative, but clinical studies have had mixed results. We hypothesized that efficient aerosolization of a surfactant with low viscosity, early in the course of RDS, could reduce the need for intubation and instillation of liquid surfactant. METHODS: A prospective, multicenter, randomized, unblinded comparison trial of aerosolized calfactant (Infasurf) in newborns with signs of RDS that required noninvasive respiratory support. Calfactant was aerosolized by using a Solarys nebulizer modified with a pacifier adapter; 6 mL/kg (210 mg phospholipid/kg body weight) were delivered directly into the mouth. Infants in the aerosol group received up to 3 treatments, at least 4 hours apart. Infants in the control group received usual care, determined by providers. Infants were intubated and given instilled surfactant for persistent or worsening respiratory distress, at their providers' discretion. RESULTS: Among 22 NICUs, 457 infants were enrolled; gestation 23 to 41 (median 33) weeks and birth weight 595 to 4802 (median 1960) grams. In total, 230 infants were randomly assigned to aerosol; 225 received 334 treatments, starting at a median of 5 hours. The rates of intubation for surfactant instillation were 26% in the aerosol group and 50% in the usual care group (P < .0001). Respiratory outcomes up to 28 days of age were no different. CONCLUSIONS: In newborns with early, mild to moderate respiratory distress, aerosolized calfactant at a dose of 210 mg phospholipid/kg body weight reduced intubation and surfactant instillation by nearly one-half.
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