Pulmonary administration of gentamicin during liquid ventilation in a newborn lamb lung injury model.

Abstract

Newborns with pulmonary infection frequently present with acute lung injury leading to ventilation/perfusion abnormalities in which intravenous delivery of antibiotics to the lung can be suboptimal. Tidal liquid ventilation (TLV) has been shown to be an effective means for delivering drugs directly to the pulmonary system. The objective of this study was to compare, with lung injury, antibiotic delivery achieved by conventional techniques (gas ventilation and intravenous gentamicin) with that using pulmonary administration of drug (PAD) during TLV. Twelve newborn lambs with an acid lung injury were randomized to receive gentamicin either intravenously during gas ventilation or via PAD during TLV using LiquiVent (Alliance Pharmaceutical Corporation, San Diego, CA, and Hoechst-Marion Roussel, Bridgewater, NJ) perfluorochemical. Gentamicin (5 mg/kg) was administered over 1 minute, and serum levels were obtained at 15-minute intervals. Arterial blood gases and pulmonary mechanics were measured. Ventilation efficiency index and arterial/alveolar oxygen ratio were calculated. Lung-tissue gentamicin levels were measured 4 hours after administration and corrected to dry weight. Serum gentamicin levels were similar in both groups. Lung gentamicin levels (micrograms/g) were significantly higher for TLV. Also, TLV resulted in significantly more of the total delivered dose in the lung after 4 hours. Ventilation efficiency index and arterial/alveolar oxygen ratios were significantly higher for TLV. In this lung injury model, both methods achieved equivalent serum gentamicin levels with higher lung levels using PAD during TLV. This study suggests that TLV may provide an effective vehicle for gentamicin delivery in infants with severe pulmonary infection and ventilation/perfusion abnormalities.