Nebulized corticosteroid in septic lung injury : An experimental study in pigs

Sammanfattning: Sepsis is occasionally complicated by the adult respiratory distress syndrome (ARDS). Auto injury by immunocompetent cells are given a central role in the pathogenesis, but our understanding of the mechanisms remains fragmentary. Treatment in septic ARDS is mainly supportive, no causal therapy exists. Mortality is high at 50-70%.The main purposes of the prese~t series of experiments in pigs were to study mechanisms involved in Gram positive and Gram negative septic lung injury, and to investigate effects of intrapulmonary delivery of nebulized drug on mediators of injury and on pulmonary integrity and function. Nebulized corticosteroid with a high anti-inflammatory activity, beclomethasone dipropionate 10 and 50 pg/kg given every 6 hours, improved gas exchange, lung mechanics, pulmonary and systemic haemodynamics and outcome for a 44 hour observation period in pigs with staphylococcal sepsis. The pulmonary effects of a corticosteroid with still higher anti-inflammatory activity, fluticasone 100pg/kg, given in endotoxaemia were similar to those seen after beclomethasone dipropionate in staphylococcal sepsis, the main difference was an increase in pulmonary artery pressures followingfluticasone. Angiotensin converting enzyme (ACE) activity in serum was analyzed and related to the stabilized systemic haemodynamics which were found in pigs treated with nebulized corticosteroid. The results indicated an association between systemic vasoregulation and ACE activity in sepsis, but they did not support that blood pressure was preserved by an ACE-dependent mechanism in corticosteroid treated pigs. Sepsis increased pulmonary sequestration of radiolabelled autologous granulocytes. This increase was significantly attenuated by nebulized beclomethasone dipropionate. The endotoxin-induced immediate accumulation of radiolabelled transferrin in the lungs, whichprobably indicated increased transcapillary protein flow, was abolished by fluticasone.In conclusion, nebulized corticosteroid given in moderate doses in sepsis reduced pulmonaty granulocyte sequestration, abolished pulmonary capillary protein leak and attenuated pulmonary dysfunction with resultant increase in survival. These protective effects of nebulized corticosteroid inexperimental septic lung injury indicate a therapeutic role in the treatment of ARDS.