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Am. J. Respir. Crit. Care Med., Volume 158, Number 3, September 1998, 840-845

Aerosolized Surfactant Improves Pulmonary Function in Endotoxin-induced Lung Injury

CHARLES LUTZ, DAVID CARNEY, CHRISTINE FINCK, ANTHONY PICONE, LOUIS A. GATTO, ANDREW PASKANIK, EDWARD LANGENBACK, and GARY NIEMAN

SUNY Health Science Center at Syracuse, Department of Surgery, Syracuse, New York; SUNY Health Science Center at Stony Brook, Stony Brook, New York; and SUNY College at Cortland, Department of Biological Sciences, Cortland, New York

Surfactant dysfunction is a primary pathophysiologic component in patients with adult respiratory distress syndrome (ARDS). In this study we tested the efficacy of aerosolized surfactant (Sf ) replacement in a severe lung injury model of endotoxin-induced ARDS. Twenty-one certified healthy pigs were anesthetized, surgically prepared for measurement of hemodynamic and lung function, then randomized into one of four groups: (1) control (n = 5), surgical instrumentation only; (2) lipopolysaccharide (LPS) (n = 6), infused with Escherichia coli LPS (100 µg/kg) without positive end- expiratory pressure (PEEP) and ventilated with a nonhumidified gas mixture of 50% N2O and 50% O2; (3) LPS + PEEP (n = 4), infused with LPS, placed on PEEP (7.5 cm H2O), and ventilated with a humidified gas mixture; and (4) LPS + PEEP + Sf (n = 6), infused with LPS, placed on PEEP, and ventilated with aerosolized Sf (Infasurf, ONY, Inc.). All animals were studied for 6 h. Arterial PO2 significantly decreased in both the LPS and LPS + PEEP groups (LPS + PEEP = 74 ± 19 mm Hg; LPS = 74 ± 19 mm Hg, p < 0.05) while venous admixture (Q S/Q T) increased in these groups (LPS + PEEP = 43.3 ± 3.9%; LPS = 47.7 ± 11%, p < 0.05) as compared with the control group. PEEP + Sf reduced the fall in PO2 (142 ± 20 mm Hg) and rise in Q S/Q T (15.1 ± 3.6%) caused by LPS. Delayed induction of PEEP (2 h following LPS) did not significantly improve any parameter over the LPS group without PEEP in this ARDS model. LPS without PEEP (3.4 ± 0.2 cells/6,400 µm2) caused a marked increase in the total number of sequestered leukocytes in the pulmonary parenchyma as compared with the control group (1.3 ± 0.1 cells/6,400 µm2). LPS + PEEP + Sf (2.3 ± 0.2 cells/6,400 µm2) significantly decreased while LPS + PEEP significantly increased (4.0 ± 0.2 cells/6,400 µm2) the total number of sequestered leukocytes as compared with the LPS without PEEP group. In summary, aerosolized surfactant replacement decreased leukocyte sequestration and improved oxygenation in our porcine model of endotoxin-induced lung injury.




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