Jet nebulization of prostaglandin E1 during neonatal mechanical ventilation:: Stability, emitted dose and aerosol particle size

Background: We have previously reported the safety of aerosolized PGE(1) in neonatal hypoxemic respiratory failure. The aim of this study is to characterize the physicochemical properties of PGE(1) solution, stability, emitted dose and the aerodynamic particle size distribution (APSD) of PGE(1) aerosol in a neonatal ventilator circuit. Methods: PGE(1) was diluted in normal saline and physicochemical properties of the solution characterized. Chemical stability and emitted dose were evaluated during jet nebulization in a neonatal conventional (CMV) or high frequency (HFV) ventilator circuit by a high performance liquid chromatography-mass spectrometry method. The APSD of the PGE(1) aerosol was evaluated with a 6-stage cascade impactor during CMV. Results: PGE(1) solution in normal saline had a low viscosity (0.9818 cP) and surface tension (60.8 mN/m) making it suitable for aerosolization. Little or no degradation of PGE(1) was observed in samples from aerosol condensates, the PGE(1) solution infused over 24 h, or the residual solution in the nebulizer. The emitted dose of PGE(1) following jet nebulization was 32-40% during CMV and 0.1% during HFV. The PGE(1) aerosol had a mass median aerodynamic diameter of 1.4 mu m and geometric S.D. of 2.9 with 90% of particles being < 4.0 mu m in size. Conclusion: Nebulization of PGE(1) during neonatal CMV or HFV is efficient and results in rapid nebulization without altering the chemical structure. On the basis of the physicochemical properties of PGE(1) solution and the APSD of the PGE(1) aerosol, one can predict predominantly alveolar deposition of aerosolized PGE(1). (c) 2007 Elsevier Ltd. All rights reserved.