Dosing and delivery of a recombinant surfactant in lung-injured adult sheep.
The purpose of this study was to evaluate a surfactant based on a recombinant surfactant protein-C (rSP-C) at three different doses (25, 100, and 200 mg lipid/kg) in the saline lavage adult sheep model of acute lung injury. All three doses resulted in significant improvements in gas exchange, although the 100 and 200 mg/kg doses were superior to the 25 mg/kg dose. There were no significant differences in effect of the 100 and 200 mg/kg doses. In addition, the physiologic efficacy and lobar surfactant distribution patterns were similar when two different surfactant delivery methods were compared. This comparison involved administering the surfactant directly into each lobe under bronchoscopic guidance, versus instilling the surfactant through an endotracheal tube into the lungs. However, the former technique took significantly longer to perform (24.5 +/- 3.3 min versus 11.6 +/- 2.5 min, p < 0.05) and required a skilled bronchoscopist. In conclusion, rSP-C surfactant was effective in improving gas exchange in this model of lung injury, although higher doses were required for optimal responses. The bronchoscopic administration technique produced results similar to those of the tracheal instillation method, but had some disadvantages that may limit the widespread clinical use of this technique in patients with lung injury.
Lewis
J
J
Department of Medicine, Lawson Research Institute, London, Ontario, Canada. jflewis@julian.uwo.ca
McCaig
L
L
Häfner
D
D
Spragg
R
R
Veldhuizen
R
R
Kerr
C
C
D000818:Animals; D001999:Bronchoscopy; D004353:Drug Evaluation, Preclinical; D007322:Instillation, Drug; D008168:Lung / Q000378:metabolism; D011510:Proteolipids / Q000008:administration & dosage* / Q000493:pharmacokinetics; D011659:Pulmonary Gas Exchange; D011663:Pulmonary Surfactants / Q000008:administration & dosage* / Q000493:pharmacokinetics; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics; D012128:Respiratory Distress Syndrome / Q000503:physiopathology / Q000628:therapy*; D012756:Sheep; D014132:Trachea
D011510:Proteolipids; D011663:Pulmonary Surfactants; D011994:Recombinant Proteins