Aerosolized and instilled surfactant therapies for acute lung injury caused by intratracheal endotoxin in rats

Objective: To compare the effects of surfactant replacement by aerosol inhalation and bolus instillation on acute lung injury caused by the intratracheal injection of endotoxin in rats. Design: Prospective, randomized study. Setting: University laboratory. Subjects: Male Wistar rats weighing 368 +/- 31 (SD) g. Interventions: Escherichia coli endotoxin 157 +/- 20 mg/kg) was injected into the tracheas of 36 anesthetized and mechanically ventilated rats (Fio(2) of 1.0). When the Pao(2) had decreased to <200 torr (<26.7 kPa), the rats were randomly assigned to one of three groups: a control group (n = 12) given no material; a bolus group (n = 12) given a modified natural surfactant suspension (100 mg/kg in 2.0 mUkg saline) by boius instillation into the trachea; and an aerosol group (n = 12) given surfactant aerosolized with an ultrasonic nebulizer for 60 mins. Measurements and Main Results: Bolus instillation transiently decreased the mean blood pressure by similar to 30%. However, aerosol inhalation did not. The pac, values of the control group remained <90 torr (<12.0 kPa) until the end of the experiment (180 mins). In contrast, the Pao(2) of the bolus group increased to 387 +/- 134 torr (51.6 +/- 17.9 kPa; p <.05 vs. other groups) 15 mins after surfactant replacement, and remained at similar to 400 torr similar to 53.3 kPa) throughout the experiment. The Pao(2) values of the aerosol group increased slowly, peaked at 240 +/- 109 torr (32.0 +/- 14.5 kPa; p <.05 vs. the control group) 60 mins after the start of surfactant replacement, and remained at similar to 200 torr (similar to 26.7 kPa). Conclusions: Bolus instillation was superior to aerosol inhalation concerning maximum efficacy, the rapid onset of therapeutic effects, and the necessary dose of surfactant. However, aerosol inhalation that does not cause hypotension may be of use in the treatment of adult respiratory distress syndrome in patients with circulatory instability.