Nebulized corticosteroid improves pulmonary function and outcome in experimental porcine septicemia

Abstract

Nebulized beclomethasone dipropionate was administered to six anesthetized and artificially ventilated pigs at 6-hourly intervals after infusion of live S. aureus (aerosol group). Changes in pulmonary mechanics, gas exchange and hemodynamics during an observation period of 44 h were compared with those in six pigs subjected to the same insults but given no corticosteroid (non-treatment group). Six pigs served as controls, without sepsis or aerosol, but with the same general management (control group). The septic insult induced an acute 3-fold increase in mean pulmonary artery pressure (MPAP) in the aerosol and non-treatment group. MPAP fell to near baseline levels in the aerosol group, but remained significantly higher in the non-treatment group. Mean systemic arterial pressure fell more in the non-treatment than in the aerosol group, reaching its lowest level at 32 h. Pulmonary function was less affected in the aerosol group, with significantly better maintenance of arterial oxygenation, lower venous admixture and superior lung-thorax compliance than in the non-treatment group. Survival was significantly improved in the aerosol group. In this porcine model of septicemia-induced adult respiratory distress syndrome, nebulized corticosteroid thus attenuated the development of respiratory failure.

Pulmonary granulocyte accumulation is reduced by nebulized corticosteroid in septic pigs

“…Pulmonary leukostasis has been associated with septic ARDS ( l ) , although the precise role of the granulocyte in the pathogenesis of the syndrome remains unclear (23). Accepting a pathogenetic role for granulocytes in this context, the decreased pulmonary accumulation of cells is consistent with the previously reported attenuation of pulmonary dysfunction in animals receiving beclomethasone dipropionate aerosol (7).…”

“…Although unlikely, since variations in cardiac output between the groups were small and non-significant throughout the study, this explanation cannot be entirely ruled out. Redistribution of flow secondary to changes in pulmonary vascular resistance, which is seen in this set-up (7), could also explain the results. An intravascular marker, such as radiolabeled erythrocytes (20), which was not employed in the present study, is required to balance the influence of these effects.…”

“…Twenty-four pigs of both sexes, median weight 21 kg, range 17 to 26 kg, were used in the experiment. The experimental set-up, which was approved by the Ethics Committee of The University Hospital of Linkoping, has been described in detail previously (7). Briefly, animals were anesthetized and prepared with tracheostomy, central venous, aortic and pulmonary artery catheters and cystostomy.…”

“…Interest has mostly been focused on neutrophils (1-3), although eosinophils (4), pulmonary macrophages (5) and platelets (6) have all been incriminated. We have previously demonstrated reduction of lung injury in septic pigs treated with intrapulmonary corticosteroid (7). Because of the likely contribution of granulocytes in the pathogenesis of lung failure, the present study was undertaken to elucidate the effects of intrapulmonary corticosteroid on accumulation of such cells in the lungs.…”

A pig model of acute Staphylococcus aureus induced pyemia

“…Models of bacteraemia, sepsis and pyemia caused by S. aureus have been established primarily in small laboratory animals (mice, rats, guinea pigs, and rabbits), while studies of experimental blood stream infection with S. aureus in pigs are few. Some of these studies in pigs aimed at the characterization of pulmonary intravascular macrophages such as the study by Winkler [ 7 ], some were models of prosthetic device infections exemplified by that reported by Paget et al [ 8 ], and some investigated the pulmonary haemodynamics and function such as those by Walther et al [ 9 , 10 ]. A few extensive studies modelling the pathogenesis of human sepsis and the ensuing shock have been performed with group A streptococci in pigs [ 11 - 14 ], but most of this type of research has been performed with Gram-negative bacteria or endotoxin [ 15 ].…”