title: Lavage administration of dilute surfactants after acute lung injury in neonatal piglets.
abstract: Exogenous surfactant therapy is not standard in the acute respiratory distress syndrome (ARDS) because of a lack of proven benefit. Nonuniform surfactant distribution after either bolus or aerosol administration may be an important factor limiting response. In a previous study of acute lung injury, we demonstrated that lavage administration of Exosurf (13.5 mg phospholipid/ml) was both effective and distributed uniformly in the lungs. Since the endogenous surfactant pool is much smaller than the typical dose of exogenous surfactant administered, we hypothesized that dilute surfactant preparations (4-4.5 mg phospholipid/ml) administered by lung lavage would be equally effective in reversing pulmonary dysfunction in a piglet model of acute lung injury. We compared three dilute surfactants: Infasurf (n = 5), KL4-Surfactant (n = 6), and Exosurf (n = 5) with controls (n = 6) and undiluted Exosurf (13. 5 mg phospholipid/ml; n = 6). All dilute surfactant preparations were effective in improving oxygenation and other parameters of pulmonary function. Surfactant administered by lavage resulted in uniform lung distribution. We conclude that dilute surfactants administered by lung lavage are effective in reversing pulmonary dysfunction after acute lung injury. We speculate that doses in the range of 20-40 mg phospholipid/kg may be adequate to improve lung function in ARDS when exogenously administered surfactant is uniformly distributed in the lung.
authors.affiliation: Department of Pediatrics, Medicine and Pathology, John A. Burns School of Medicine, University of Hawaii and Kapiolani Medical Center for Women and Children, Honolulu, HI 96826, USA.
authors.forename: V
authors.initials: V
authors.lastname: Balaraman
authors.forename: J
authors.initials: J
authors.lastname: Meister
authors.forename: T L
authors.initials: TL
authors.lastname: Ku
authors.forename: S L
authors.initials: SL
authors.lastname: Sood
authors.forename: E
authors.initials: E
authors.lastname: Tam
authors.forename: J
authors.initials: J
authors.lastname: Killeen
authors.forename: C F
authors.initials: CF
authors.lastname: Uyehara
authors.forename: E
authors.initials: E
authors.lastname: Egan
authors.forename: D
authors.initials: D
authors.lastname: Easa
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D018893:Bronchoalveolar Lavage; D004195:Disease Models, Animal; D004338:Drug Combinations; D005233:Fatty Alcohols / Q000008:administration & dosage / Q000627:therapeutic use; D036341:Intercellular Signaling Peptides and Proteins; D008171:Lung Diseases / Q000188:drug therapy*; D010455:Peptides / Q000008:administration & dosage / Q000627:therapeutic use; D010767:Phosphorylcholine; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000627:therapeutic use; D011663:Pulmonary Surfactants / Q000008:administration & dosage* / Q000627:therapeutic use; D012128:Respiratory Distress Syndrome; D013552:Swine
chemical_list: D004338:Drug Combinations; D005233:Fatty Alcohols; D036341:Intercellular Signaling Peptides and Proteins; C097558:KL4 surfactant; D010455:Peptides; D011663:Pulmonary Surfactants; D010767:Phosphorylcholine; D011092:Polyethylene Glycols; C047049:dipalmitoylphosphatidylcholine, hexadecanol, tyloxapol drug combination