Abstract 1943

Newborns with acute lung injury often present with sepsis. Of these patients, many are also candidates for PLV. We hypothesized that a nanocrystal (G) perfluorochemical (PFC) suspension of (G/PFC) delivered IT to the lungs could be homogeneously distributed at lower serum levels than IV delivery. Also, we sought to compare G serum, G lung levels & physiological responses when IT G/PFC was delivered at the start of PLV vs. during PLV. To test this hypothesis, 17 lambs were ventilated by PLV with perflubron (FRC= 20ml/kg, PIP/PEEP= 10-20/3-5 cm H2O, IMV=20-35 br/min, FiO2=1.0) for 4 hrs using 3 different delivery approaches of G (5mg/kg): IT slow fill SF (n=6; G/PFC over 15 mins at start of PLV), IT bolus B (n=6; G/PFC 5-30 mins after start of PLV), IV (n=5; aqueous injection at start of PLV). Throughout the study serum G levels, arterial blood gases (mmHg), compliance (CDyn ml/cmH2O/kg) and mean blood pressure (MAP mmHg) were measured. Reported serum levels were time-averaged and lung G levels were measured at 4 hours and averaged across lobes. All data are expressed as means±SEM; p<0.05. Throughout the study pH (7.42±0.01), pCO2 (38±0.7), pO2(336±11), CDyn (0.91±0.10), and MAP (76±0.9) were safely maintained across all groups. Differences in serum G were: IV> B>SF. Lung tissue G showed SF>B>IV. Analysis of individual lobes showed that lung G distribution was homogeneous where SF>B>IV with respect to intra-lobar uniformity. These results demonstrate that IT delivery of a nanocrystal suspension of G/PFC is effective at the start of PLV or after the lung is filled with PFC. Both IT methods provide higher lung levels when compared to IV G and maintain low serum G levels. These findings suggest that for a given dose of G, the delivery method of G/PFC suspension can facilitate pulmonary relative to systemic antibiotic coverage.Table

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Funded in part by Alliance Pharm Corp., Sharpe Research Foundation