2011 OPEN FORUM Abstracts
AEROSOLIZED KL4 SURFACTANT IMPROVES GAS EXCHANGE AND SURVIVAL IN SPONTANEOUSLY BREATHING PIGLETS WITH HCL INDUCED ACUTE LUNG INJURY.
Patricia A. Meyers1, Cathy Worwa1, Brenda Plumm1, Andrea L. Lampland1,4, Mark C. Mammel1,4, Marla R. Wolfson2, Christopher Henderson3, Timothy Gregory3; 1Infant Diag. & Research Center, Children's Hospitals & Clinics of Minnesota, St. Paul, MN; 2Physiology, Temple University, Philadelphia, PA; 3Discovery Labs, Inc., Warrington, PA; 4Pediatrics, University of Minnesota, Minneapolis, MN
Background: Surfactant therapy may be a useful treatment for acute lung injury (ALI) (Pediatric Pulmonol 2010;68:782). Use of aerosolized surfactant in ALI has not been investigated. Objective: Evaluate aerosolized surfactant (KL4; lucinactant, Discovery Laboratories, Inc., Warrington, PA) in treating piglets with HCl-induced ALI. Design/Methods: ALI was induced in spontaneously breathing piglets with intratracheal 0.2N HCl until PaO2 was ≤ 350 torr at FiO2 1.0. Piglets were randomized to receive 5.8 ml/kg (175 mg/kg) of endotracheal KL4 (ET KL4) with extubation to CPAP; aerosolized KL4 (AERO KL4; 60 minutes; 22.5 mg/min) while on CPAP; or CPAP alone (CPAP/control). Piglets were monitored for 3 hours; blood gases obtained every 30 minutes. Lung tissue was analyzed for IL-8 and total protein by porcine-specific ELISA and Bradford with group differences analyzed by ANOVA. Physiologic data were analyzed using 2 way ANOVA with Tukey LSD post-hoc testing for p values < 0.05. Results: Both ET KL4 and AERO KL4 produced higher PaO2s (p < 0.001) and improved survival (p < 0.05) compared to CPAP. AERO KL4 was as effective as ET KL4, and produced the highest final PaO2 (p < 0.05). IL-8/total protein ratios were lower in AERO KL4 versus CPAP (p < 0.03). Conclusions: In spontaneously breathing piglets with ALI, AERO KL4 and ET KL4 resulted in better gas exchange and survival. AERO KL4 was as effective as ET KL4, and produced the highest final PaO2. AERO KL4 treated piglets had lower IL-8/total protein ratios than CPAP, suggesting less lung inflammation. This is the first successful use of aerosolized surfactant in an animal model of ALI.
Sponsored Research - Discovery Laboratories, Inc., Warrington, PA
P < 0.001 compared to controls