Surfactant (SF) Delivery with Conventional Mechanical Ventilation (CMV) and Partial Liquid Ventilation (PLV) in Meconium Aspiration Injury

Abstract 1750 Poster Session IV, Tuesday, 5/4 (poster 340)

Evidence of SF inactivation by meconium has led to the use of exogenous SF administration in the management of meconium aspiration syndrome (MAS). PLV ^SM has also been efficacious in the management of MAS. In addition, perfluorochemical (PFC) liquids have been shown to be effective vehicles for pulmonary administration of drugs (PAD) during liquid ventilation. We hypothesized that PLV would facilitate the delivery of SF in a MAS model. The objective of this study was to compare SF delivery using conventional techniques (intratracheal instillation during CMV) with that using PAD during PLV. Surfactant delivery was evaluated in 2 groups of adult rats after a meconium instillation of 2.5 ml/kg (20% v/w): GR I: (N=6) CMV; GR II: (N = 7) PLV. C₁₄ labeled SF (Survanta®; 4 ml/kg) was delivered intratracheally in 4 aliquots over 20 min in both groups. Animals were positioned during delivery so as to optimize distribution. In GR II, a dose of perflubron (LiquiVent®; 20 ml/kg) was instilled via infusion pump during the 20 min surfactant delivery. Surfactant distribution and physiological responses were evaluated. At the conclusion of the experiment, lungs were inflated (30 cm H₂O), dried, sectioned, and evaluated for radioactivity in disintegrations per min. Surfactant distribution was better with PLV as compared to CMV: 48.8% of the pieces vs 30.9% of the pieces received within 25% of the mean amount of SF, respectively. Further, regional distribution was also significantly more uniform with PLV: left (p < 0.01) vs right (p <0.01) lung and ventral (p < 0.01) vs dorsal (p < 0.01) regions. PaO₂ and the ventilation efficiency index were significantly greater for PLV vs CMV treatments. These data demonstrate that perflubron delivery of SF is more effective than conventional delivery in a MAS model. Furthermore, these studies suggest the utility of PLV/SF combinational therapy for treatment of other etiologies of neonatal respiratory distress.

[Funded in part by Alliance Pharmaceutical Corporation]