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-expirat ory pressure (PEEP). Design: Prospective trial. Setting: Laboratory at a university medical center. Subjects: Nineteen certified healthy pig s, weighing 15 to 20 kg. Interventions: Pigs were anesthetized and sur gically prepared for hemodynamic and lung function measurements. Anima ls were randomized into four groups: a) Control pigs (n = 4) received an intravenous infusion of saline without Escherichia coli lipopalysac charide (LPS); b) the LPS group (n = 5) received an intravenous infusi on of saline containing LPS (100 mu g/kg); c) the PEEP plus saline gro up (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 a n intravenous infusion of saline containing LPS. Two hours following L PS 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 po sitive pressure ventilation. All groups were studied for 6 hrs after t he start of LPS injection. At necropsy, bronchoalveolar lavage was per formed and the right middle lung lobe was fixed for histologic analysi s. Measurements and Main Results: Compared with LPS without treatment, PEEP plus surfactant significantly increased PaO2 (PEEP plus surfacta nt = 156.6 +/- 18.6 [SEM] toll [20.8 +/- 2.5 kPa]; LPS = 79.2 +/- 21.9 torr [10.5 +/- 2.9 kPa]; p <.05), and decreased venous admixture (PEE P 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 LP S infusion. PEEP plus surfactant did not alter ventilatory efficiency index (VEI = 3800/[peak airway pressure - PEEP] respiratory rate . Pac O(2)), or static compliance as compared with LPS without treatment at any time point. Cytologic analysis of bronchoalveolar lavage fluid sho wed that surfactant treatment significantly increased the percentage o f alveolar neutrophils as compared with LPS without treatment (PEEP pl us 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 se questered leukocytes (LPS group = 3.4 +/- 0.2 cells/6400 mu(2); centra l group = 1.3 +/- 0.1 cells/6400 mu(2); p<.05). PEEP plus saline and P EEP plus surfactant significantly increased the total number of seques tered leukocytes in the pulmonary parenchyma (PEEP plus surfactant = 8 .2 +/- 0.7 cells/6400 mu(2); PEEP plus saline = 3.9 +/- 0.2 cells/6400 mu(2); 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 maintai n this salutary effect indefinitely. Thus, repeat bolus dosing of surf actant or bolus treatment followed by continuous aerosol delivery may be necessary for a continuous beneficial effect.