Aerosolized surfactant in neonatal respiratory distress syndrome: Phase I study

Beena G Sood; Josef Cortez; Madhuri Kolli; Amit Sharma; Virginia Delaney-Black; Xinguang Chen

doi:10.1016/j.earlhumdev.2019.05.005

Aerosolized surfactant in neonatal respiratory distress syndrome: Phase I study

Early Hum Dev. 2019 Jul:134:19-25. doi: 10.1016/j.earlhumdev.2019.05.005. Epub 2019 May 20.

Authors

Beena G Sood¹, Josef Cortez², Madhuri Kolli³, Amit Sharma⁴, Virginia Delaney-Black⁵, Xinguang Chen⁶

Affiliations

¹ Children's Hospital of Michigan, 3901 Beaubien Blvd., Suite 3N027, Detroit, MI 48201, USA; Hutzel Women's Hospital, 3990 John R St, Detroit, MI 48201, USA; Department of Pediatrics, Wayne State University School of Medicine, 540 E Canfield St, Detroit, MI 48201, USA. Electronic address: bsood@med.wayne.edu.
² Department of Pediatrics, University of Florida College of Medicine, 665 W 8th Street, Jacksonville, FL 32209, USA. Electronic address: Josef.Cortez@jax.ufl.edu.
³ Department of Pediatrics, Wayne State University School of Medicine, 540 E Canfield St, Detroit, MI 48201, USA.
⁴ Children's Hospital of Michigan, 3901 Beaubien Blvd., Suite 3N027, Detroit, MI 48201, USA; Hutzel Women's Hospital, 3990 John R St, Detroit, MI 48201, USA; Department of Pediatrics, Wayne State University School of Medicine, 540 E Canfield St, Detroit, MI 48201, USA. Electronic address: asharma2@dmc.org.
⁵ Department of Pediatrics, Wayne State University School of Medicine, 540 E Canfield St, Detroit, MI 48201, USA. Electronic address: vdelaney@med.wayne.edu.
⁶ University of Florida College of Medicine, College of Public Health, 2004 Mowray Road, Gainesville, FL 32610, USA. Electronic address: jimax.chen@ufl.edu.

PMID: 31121339
DOI: 10.1016/j.earlhumdev.2019.05.005

Abstract

Background: Treating respiratory distress syndrome (RDS) with intratracheal surfactant requires endotracheal intubation and mechanical ventilation, (MV) with their attendant risks. Use of non-invasive respiratory support in the delivery room averts the need for MV but delays surfactant administration.

Objective: We hypothesized that aerosolized surfactant is feasible and safe in infants 24^0/7-36^6/7 weeks gestational age (GA) with RDS, receiving non-invasive respiratory support.

Design/methods: In an unblinded Phase I study, sequentially enrolled infants with RDS stratified by GA received increasing doses (100 or 200 mg/kg of phospholipid) and dilutions (12.5 or 8.3 mg/ml) of surfactant using a jet nebulizer. Infants were monitored clinically and with cerebral oximetry.

Results: Seventeen infants were enrolled. Age at start of first dose and dose duration were 4.9 (3.4-10.1) and 2.1 (1.0-2.8) hours respectively. Two infants in the lowest GA stratum (24^0/7-28^6/7) required intubation within 2 h after the first dose. Fifteen infants completed the study; 13 received two doses. Infants tolerated the aerosol treatment well. No other significant adverse events were identified. Parental permission for cerebral oximetry was obtained in 16 infants. In the two infants who later exited the study, values prior to start of aerosolized surfactant were lower compared to 14 infants who completed the study (p = 0.0835), increased after start of study intervention (p = 0.0105) and decreased after intubation (p = 0.0003).

Conclusions: We have demonstrated the feasibility and safety of aerosolized surfactant in preterm infants receiving non-invasive respiratory support. The treatment was well tolerated by infants and clinical caregivers.

Keywords: Aerosol; Aerosolized surfactant; Nebulizer; Prematurity; Respiratory distress syndrome; Surfactant; Ventilation.

Publication types

Clinical Trial, Phase I
Research Support, Non-U.S. Gov't

MeSH terms

Administration, Inhalation*
Female
Humans
Infant, Newborn
Male
Nebulizers and Vaporizers
Pulmonary Surfactants / administration & dosage*
Pulmonary Surfactants / adverse effects
Pulmonary Surfactants / therapeutic use
Respiratory Distress Syndrome, Newborn / drug therapy*

Substances

Pulmonary Surfactants