Inhibition of pulmonary surfactant function by meconium

Plasma concentrations of inflammatory cytokines rise rapidly during ECMO-related SIRS due to the release of preformed stores in the intestine

Extracorporeal membrane oxygenation (ECMO) is an important life-support system used in neonates and young children with intractable cardiorespiratory failure. In this study, we used our porcine neonatal model of venoarterial ECMO to investigate whether ECMO causes gut barrier dysfunction. We subjected 3-wk-old previously healthy piglets to venoarterial ECMO for up to 8 h and evaluated gut mucosal permeability, bacterial translocation, plasma levels of bacterial products, and ultrastructural changes in gut epithelium. We also measured plasma lipopolysaccharide (LPS) levels in a small cohort of human neonates receiving ECMO. In our porcine model, ECMO caused a rapid increase in gut mucosal permeability within the first 2 h of treatment, leading to a 6- to 10-fold rise in circulating bacterial products. These changes in barrier function were associated with cytoskeletal condensation in epithelial cells, which was explained by phosphorylation of a myosin II regulatory light chain. In support of these findings, we also detected elevated plasma LPS levels in human neonates receiving ECMO, indicating a similar loss of gut barrier function in these infants. On the basis of these data, we conclude that ECMO is an independent cause of gut barrier dysfunction and bacterial translocation may be an important contributor to ECMO-related inflammation.

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Extracorporeal membrane oxygenation causes loss of intestinal epithelial barrier in the newborn piglet.

Meconium aspiration syndrome (MAS) is a frequent cause of respiratory distress in term infants. Recent reports suggested that surfactant dysfunction contributes to the pathophysiology of MAS. In the present study, we assessed the effect of three different concentrations of surfactant suspensions in the lavage fluid of a rabbit model of MAS. Young animals were given 5 mL/kg of a 20% slurry of human meconium into the endotracheal tube and were then mechanically ventilated. The animals were divided into four groups receiving lavage fluids with either saline or surfactant suspensions (2.5 mg/mL, 5 mg/mL, and 10 mg/mL). Lavage was performed an hour after meconium instillation with one of the four solutions at 10 mL/kg in three divided doses. After lavage, the total amount of meconium recovered was measured.



The 10 mg/mL surfactant lavage group had the best improvement in gas exchange, whereas the saline group had no improvement. The amount of meconium recovered was the best in the 10 mg/mL surfactant group among the four groups studied. On histologic examination, alveolar inflammation was less evident in the surfactant lavage groups than in the saline lavage group.



It was concluded that lavage with surfactant solution at a concentration of 10 mg/mL washed out meconium most effectively, and improved gas exchange and lung histology in the rabbit model of MAS more than saline lavage. Pediatr Pulmonol. 1999; 28:18–23. © 1999 Wiley-Liss, Inc.

Treatment of meconium aspiration syndrome with surfactant lavage in an experimental rabbit model

Meconium aspiration syndrome (MAS) is a frequent cause of respiratory distress in neonates. Recent reports have suggested that surfactant dysfunction contributes to the pathophysiology of MAS and surfactant therapy improves oxygenation of infants with MAS. We evaluated the effect of bronchial lavage with surfactant solution in a rabbit model of meconium aspiration. All animals were given 5 mL/kg of a 20% slurry of human meconium into the endotracheal tube and mechanically ventilated. The animals were then divided into saline lavage (n = 5) or surfactant lavage (n = 5). Lavage was performed an hour after meconium instillation. After the lavage the total amount of meconium recovered was measured. Blood gas was monitored during the experiment. The amount of meconium recovered by saline lavage was 14%, and by surfactant lavage was 57%. The surfactant group had a significant improvement in gas exchange, whereas the saline group had no improvement. It was concluded that the lavage with surfactant solution effectively washed out meconium and improved gas exchange in rabbit model of MAS.

Effect of surfactant lavage in a rabbit model of meconium aspiration syndrome.

Meconium aspiration syndrome (MAS) is a common cause of morbidity and mortality in neonates Chemical pneumonitis can lead to persistent pulmonary hypertension of the newborn (PPHN) with irreversible hypoxia and death Extracorporeal membrane oxygenation (ECMO) for the treatment of severe PPHN became available at the Ochsner Foundation Hospital in September 1983 We reviewed the first 28 cases in which ECMO was used for the treatment of PPHN due to severe MAS; 26 of the 28 infants survived During the three years preceding our development of ECMO capability, ten neonates had PPHN due to severe MAS and met the criteria for ECMO; only three survived The difference in survival demonstrates the efficacy of ECMO for the treatment of severe MAS We believe that when established criteria are met, ECMO should be instituted without delay

Extracorporeal membrane oxygenation as treatment of severe meconium aspiration syndrome.

The various combinations of varicose veins, limb hypertrophy, and hemangiomas necessitate diagnostic consideration of the Klippel-Trenaunay syndrome versus Weber's syndrome and cavernous hemangioma. The wide spectrum of this disease has generated diverse approaches, and treatment must be individualized. Whereas the Klippel-Trenaunay syndrome is rarely a surgical disease, the gigantic proportions of our patient's anomaly warranted prompt amputation.

Robert M. Arensman

Papers

Extracorporeal membrane oxygenation as treatment of severe meconium aspiration syndrome.

Klippel-Trenaunay syndrome: rarely a surgical disease.