Aerosolized and instilled surfactant therapies for acute lung injury caused by intratracheal endotoxin in rats
Tashiro, K.; Yamada, K.; Li, W.Z.; Matsumoto, Y.; Kobayashi, T.
Critical Care Medicine 24(3): 488-494
1996
ISSN/ISBN: 0090-3493 PMID: 8625639 Document Number: 467387
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 (57 +- 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 lt 200 torr ( lt 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 mL/kg saline) by bolus 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 apprx 30%. However, aerosol inhalation did not. The Pao-2 values of the control group remained lt 90 torr ( lt 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 lt .05 vs. other groups) 15 mins after surfactant replacement, and remained at apprx 400 torr ( apprx 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 lt .05 vs. the control group) 60 mins after the start of surfactant replacement, and remained at apprx 200 torr ( apprx -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.