Surface Tension of Therapeutic Surfactants (Exosurf Neonatal, Infasurf, and Survanta) as Evaluated by Standard Methods and Criteria

ABSTRACT

Three commercial preparations for the treatment of neonatal respiratory distress syndrome (NRDS), Exosurf Neonatal (EX), Infasurf (IN), and Survanta (SU), were studied at 37°C in both a pulsating bubble surfactometer and a vertical film surface balance. “Static” characteristics of adsorbed films were assessed with “bubble” at maximum radius (R_max) and at minimum radius (R_min). Adsorption time was time to stable film formation (γ equilibrium). In dynamic experiments, the bubble was cycled (compressed-decompressed) between R_max and R_min at 20, 40, and 80 cpm. Spread films were cycled in the surface balance between maximum area (A_max) and minimum area (A_min) at 1.5 cpm. In all experiments, maximum surface tension (γmax) coincided with R_max or A_max and γmin with R_min or A_min. All trials were continued until γmax and γmin were reproducible. Data were evaluated according to standard criteria for normal function both in vivo and in vitro of lipid mixtures (EX) or natural surfactants (IN, SU) prepared for treatment of NRDS. All preparations failed two of the four criteria, adsorption in the time of a deep breath and maintenance of stable, low γ. Adsorption required 10 to 20 seconds and stable γ was achieved only at equilibrium γ, > 17 mN/m. IN and SU conformed in general to two criteria, γ approaching zero on compression and low surface compressibility (<0.09 m/mN), whereas spontaneously formed films of EX did not. EX was idiosyncratic in that these two criteria were met only after an apparent change of film conformation had been effected, possibly related to elimination of preparation additives from the surface. Our studies lead to the conclusion that these preparations, particularly EX, do not establish normal surfactant function. Other considerations are that the established criteria do not define normal surfactant function and that conventional in vitro models (assay methods) do not reliably represent conditions at the alveolar surface.