EFFECT OF SINGLE VS. MULTIPLE DOSING ON PERFLUOROCHEMICAL (PFC) ELIMINATION PROFILE DURING PARTIAL LIQUID VENTILATION WITH LIQUIVENT®. † 2029

Previously, PFC elimination during partial liquid ventilation (PLV) has been qualitatively estimated from theoretical calculations, radiographic assessment, and visualization of PFC in the endotracheal tube at zero end expiratory pressure. The objective of this study was to quantitate PFC elimination kinetics following initial fill and with or without hourly dosing. Eleven adolescent New Zealand rabbits (1.55 ± 0.05 SE kg) were surgically instrumented and studied in two groups: Gr I: (n=6) PLV with LiquiVent® (S: single dose); Gr II: (n=5) PLV with LiquiVent® and hourly dosing (M: multiple doses). All rabbits were studied for four hours following initial instillation of PFC liquid (17 ± 0.72 SE ml/kg) equal to the measured gas functional residual capacity. Animals were ventilated at constant breathing frequency (30 bpm), tidal volume (9.3 ± 0.3 SE ml/kg), positive end expiratory pressure (4 cmH₂O), inspiratory time(0.3 sec), and temperature (33 °C). PFC saturation of mixed expired gas(PFC-Sat) was assessed with a thermal conductivity analyzer and PFC elimination was calculated from PFC-Sat, minute ventilation, and temperature. For the M group additional doses were determined via hourly PFC elimination calculations. Arterial blood gases and lung mechanics were also assessed. PFC elimination data (mean ± SE) during 4 hrs of study are tabulated below:Table Results of this study demonstrate an appreciable increase in PFC-Sat and PFC elimination over time from the respiratory system with hourly supplementation when compared to animals which did not receive additional doses (p < 0.05). Additionally, PFC loss decreases with time independent of group (p < 0.05). These data demonstrate that PFC elimination rate is not constant and follows a non-linear decrement with time. This may have occurred due to distributional differences of ventilation and PFC between the M and S groups. These data are relevant in that the protective benefit of PFC in the lung may be sustained by frequent dosing which maintains PFC lung volume. (Supp. in part by NIH grant # R29HD26341 and Alliance Pharm. Corp.)

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