Effects of surfactant distribution and ventilation strategies on efficacy of exogenous surfactant.

The effects of both surfactant distribution patterns and ventilation strategies utilized after surfactant administration were assessed in lung-injured adult rabbits. Animals received 50 mg/kg surfactant via intratracheal instillation in volumes of either 4 or 2 ml/kg. A subset of animals from each treatment group was euthanized for evaluation of the exogenous surfactant distribution. The remaining animals were randomized into one of three ventilatory groups: group 1 [tidal volume (VT) of 10 ml/kg with 5 cmH2O positive end-expiratory pressure (PEEP)]; group 2 (VT of 5 ml/kg with 5 cmH2O PEEP); or group 3 (VT of 5 ml/kg with 9 cmH2O PEEP). Animals were ventilated and monitored for 3 h. Distribution of the surfactant was more uniform when it was delivered in the 4 ml/kg volume. When the distribution of surfactant was less uniform, arterial PO2 values were greater in groups 2 and 3 compared with group 1. Oxygenation differences among the different ventilation strategies were less marked in animals with the more uniform distribution pattern of surfactant (4 ml/kg). In both surfactant treatment groups, a high mortality was observed with the ventilation strategy used for group 3. We conclude that the distribution of exogenous surfactant affects the response to different ventilatory strategies in this model of acute lung injury.

Effects of ventilation strategies on the efficacy of exogenous surfactant therapy in a rabbit model of acute lung injury.

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.