Effects of Ventilation Strategies on the Efficacy of Exogenous Surfactant Therapy in a Rabbit Model of Acute Lung Injury

• DOI: 10.1164/ajrccm.157.1.9701073
• Publication Date: 2013-04-04T17:30:55Z
• Authors: YUSHI ITO; STUART E. E. MANWELL; CAROLYN L. KERR; RUUD A. W. VELDHU...; LI-JUAN YAO; DAVE BJARNESON; LYNDA A. McCAIG; ADRIENNE J. BARTLETT; JAMES F. LEWIS
• Keywords: Respiratory Distress Syndrome; Drug Evaluation, Preclinical; Pulmonary Surfactants; Sodium Chloride; Positive-Pressure Respiration; Disease Models, Animal; Random Allocation; 03 medical and health sciences; 0302 clinical medicine; Tidal Volume; Animals; Cattle; Rabbits; Blood Gas Analysis; Therapeutic Irrigation; Bronchoalveolar Lavage Fluid

We evaluated the effects of various ventilation strategies on the efficacy of exogenous surfactant therapy in lung-injured adult rabbits. Lung injury was induced by repetitive whole-lung saline lavage followed by mechanical ventilation. Three hours after the final lavage, 100 mg lipid/kg bovine lipid extract surfactant was instilled. After confirmation of similar responses to exogenous surfactant, animals were then randomized to one of four ventilation groups; (1) Normal tidal volume (VT) (5 cm H2O): VT = 10 ml/kg, respiratory rate (RR) = 30/min, positive end-expiratory pressure (PEEP) = 5 cm H2O; (2) Normal VT (9 cm H2O): VT = 10 ml/kg, RR = 30/min, PEEP = 9 cm H2O; (3) Low VT (5 cm H2O): VT = 5 ml/kg, RR = 60/min, PEEP = 5 cm H2O; (4) Low VT (9 cm H2O): VT = 5 ml/kg, RR = 60/min, PEEP = 9 cm H2O. Animals were ventilated for an additional 3 h and then killed, and lung lavage fluid was analyzed. Animals ventilated with the low-VT modes (Low VT [5 cm H2O] and Low VT [9 cm H2O]) had higher PaO2 values (430 +/- 7 mm Hg and 425 +/- 18 mm Hg versus 328 +/- 13 mm Hg) and higher percentages of surfactant in large aggregate forms (83 +/- 2% and 82 +/- 2% versus 67 +/- 4%) at 3 h after treatment than did the Normal VT (5 cm H2O) group (p < 0.05). Increasing the PEEP level was beneficial for a short period after surfactant administration to maintain oxygenation, but did not affect exogenous surfactant aggregate conversion. We speculate that ventilation strategies resulting in low exogenous surfactant aggregate conversion will result in superior physiologic responses to exogenous surfactant.