Exogenous surfactant and positive end-expiratory pressure in the treatment of endotoxin-induced lung injury

OBJECTIVE: To evaluate the efficacy of treating endotoxin-induced lung injury with single dose exogenous surfactant and positive end-expiratory pressure (PEEP). DESIGN: Prospective trial. SETTING: Laboratory at a university medical center. SUBJECTS: Nineteen certified healthy pigs, weighing 15 to 20 kg. INTERVENTIONS: Pigs were anesthetized and surgically prepared for hemodynamic and lung function measurements. Animals were randomized into four groups: a) Control pigs (n = 4) received an intravenous infusion of saline without Escherichia colilipopolysaccharide (LPS); b) the LPS group (n = 5) received an intravenous infusion of saline containing LPS (100 microg/kg); c) the PEEP plus saline group (n = 5) received an intravenous infusion of saline containing LPS. Two hours after LPS infusion, saline was instilled into the lung as a control for surfactant instillation, and the animals were placed on 7.5 cm H2O of PEEP; d) the PEEP plus surfactant group (n = 5) received an intravenous infusion of saline containing LPS. Two hours following LPS infusion, surfactant (50 mg/kg) was instilled into the lung and the animals were placed on 7.5 cm H2O of PEEP. PEEP was applied first and surfactant or saline was instilled into the lung while maintaining positive pressure ventilation. All groups were studied for 6 hrs after the start of LPS injection. At necropsy, bronchoalveolar lavage was performed and the right middle lung lobe was fixed for histologic analysis. MEASUREMENTS AND MAIN RESULTS: Compared with LPS without treatment, PEEP plus surfactant significantly increased PaO2 (PEEP plus surfactant = 156.6 +/- 18.6 SEM] torr 20.8 +/- 2.5 kPa]; LPS = 79.2 +/- 21.9 torr 10.5 +/- 2.9 kPa]; p<.05), and decreased venous admixture (PEEP plus surfactant = 12.5 +/- 2.0%; LPS = 46.9 +/- 14.2%; p< .05) 5 hrs after LPS infusion. These changes were not significant 6 hrs after LPS infusion. PEEP plus surfactant did not alter ventilatory efficiency index (VEI = 3800/peak airway pressure - PEEP] x respiratory rate x PacO2), or static compliance as compared with LPS without treatment at any time point. Cytologic analysis of bronchoalveolar lavage fluid showed that surfactant treatment significantly increased the percentage of alveolar neutrophils as compared with LPS without treatment (PEEP plus surfactant = 39.1 +/- 5.5%; LPS = 17.4 +/- 6.6%; p< .05). Histologic analysis showed that LPS caused edema accumulation around the airways and pulmonary vessels, and a significant increase in the number of sequestered leukocytes (LPS group = 3.4 +/- 0.2 cells/6400 micro2; control group = 1.3 +/- 0.1 cells/6400 micro2; p < .05). PEEP plus saline and PEEP plus surfactant significantly increased the total number of sequestered leukocytes in the pulmonary parenchyma (PEEP plus surfactant = 8.2 +/- 0.7 cells/6400 micro2; PEEP plus saline = 3.9 +/- 0.2 cells/6400 micro2; p <.05) compared with the control and LPS groups. CONCLUSIONS: We conclude that PEEP plus surfactant treatment of endotoxin-induced lung injury transiently improves oxygenation, but is unable to maintain this salutary effect indefinitely. Thus, repeat bolus dosing of surfactant or bolus treatment followed by continuous aerosol delivery may be necessary for a continuous beneficial effect.