Sildenafil prevents the increase of extravascular lung water and pulmonary hypertension after meconium aspiration in newborn piglets

Meconium aspiration syndrome causes respiratory failure after birth and in vivo monitoring of pulmonary edema is difficult. The objective of the present study was to assess hemodynamic changes and edema measured by transcardiopulmonary thermodilution in low weight newborn piglets. Additionally, the effect of early administration of sildenafil (2 mg/kg vo, 30 min after meconium aspiration) on this critical parameter was determined in the meconium aspiration syndrome model. Thirty-eight mechanically ventilated anesthetized male piglets (Sus scrofa domestica) aged 12 to 72 h (1660 ± 192 g) received diluted fresh human meconium in the airway in order to evoke pulmonary hypertension (PHT). Extravascular lung water was measured in vivo with a PiCCO monitor and ex vivo by the gravimetric method, resulting in an overestimate of 3.5 ± 2.3 mL compared to the first measurement. A significant PHT of 15 Torr above basal pressure was observed, similar to that of severely affected humans, leading to an increase in ventilatory support. The vascular permeability index increased 57 percent, suggesting altered alveolocapillary membrane permeability. Histology revealed tissue vessel congestion and nonspecific chemical pneumonitis. A group of animals received sildenafil, which prevented the development of PHT and lung edema, as evaluated by in vivo monitoring. In summary, the transcardiopulmonary thermodilution method is a reliable tool for monitoring critical newborn changes, offering the opportunity to experimentally explore putative therapeutics in vivo. Sildenafil could be employed to prevent PHT and edema if used in the first stages of development of the disease.

Inflammatory markers in meconium induced lung injury in neonates and effect of steroids on their levels: a randomized controlled trial.

PURPOSE: To determine the levels of TNFa and IL-1beta in tracheal aspirates of neonates with meconium aspiration syndrome (MAS) and to ascertain whether the use of steroids by systemic or nebulized routes suppresses the levels of these inflammatory markers. METHODS: This was a double blind, randomized, controlled, prospective, interventional study done over one year period in the neonatal unit of the Lady Hardinge Medical College. Fifty-one babies of MAS which were randomly distributed into three groups; control, systemic and nebulized steroids; were included in the study. Methyl prednisolone was given intravenously in the dosage of 0.5 mg/kg/day in two divided doses while nebulized budecort was given in a dosage of 50 mcg/dose twice daily. Tracheal aspirates were taken on day 1, 3 and 4 and were analyzed for TNFa and IL-1b by ELISA technique. RESULTS: TNFa in tracheal aspirates showed an increasing trend in babies of MAS in first four days, thereby signifying an inflammatory process underlying the condition. The levels of TNFa were suppressed by use of steroids. Higher levels of TNFa were associated with longer stay in hospital. IL-1b did not show any significant correlation. CONCLUSIONS: TNFa is associated with meconium-associated inflammation. Its level is suppressed with the use of steroids and can also be used to assess prognosis of neonates with MAS.

Different doses of exogenous surfactant for treatment of meconium aspiration syndrome in newborn rabbits

OBJETIVO: Avaliar os efeitos de duas diferentes doses de surfactante exógeno sobre a mecânica pulmonar e sobre a regularidade da expansão do parênquima pulmonar em coelhos recém-nascidos. MÉTODO: Coelhos recém-nascidos foram traqueostomizados e randomizados em quatro grupos de estudo: grupo-Controle, sem aspiração de mecônio; grupo MEC, com aspiração de mecônio e sem tratamento com surfactante exógeno; grupos S100 e S200, ambos com aspiração de mecônio e tratados respectivamente com 100 e 200 mg/kg de surfactante exógeno (produzido e fornecido pelo Instituto Butantan). Os animais dos 4 grupos foram ventilados por 25 minutos. A mecânica pulmonar foi avaliada a partir dos valores de complacência dinâmica, pressão ventilatória, volume-corrente e volume pulmonar máximo (curva P-V). A análise histológica foi feita calculando-se o diâmetro alveolar médio (Lm) e o índice de distorção através do desvio padrão do Lm. Utilizou-se ANOVA One Way com a = 0,05. RESULTADOS: Após 25 minutos de ventilação, os valores de complacência dinâmica (ml/cm H2O.kg) foram: 0,87± 0,07 (Controle); 0,49±0,04 (MEC*); 0,67±0,06 (S100) e 0,67±0,08 (S200) e de pressão ventilatória (cm H2O): 9,0± 0,9 (Controle); 16,5±1,7 (MEC*); 12,4±1,1 (S100) e 12,1±1,5 (S200). Ambos os grupos tratados tiveram padrão de expansão do parênquima mais homogêneo em relação aos animais não tratados: índice de distorção de 7,5± 1,9 (Controle); 11,3±2,5 (MEC*); 5,8±1,9 (S100) e 6,7±1,7 (S200) (*p < 0,05 vs outros grupos). CONCLUSÕES: Animais tratados com surfactante mostraram melhora significativa da mecânica pulmonar e maior homogeneidade do padrão de expansão pulmonar comparados ao grupo não tratado. Não houve influência das doses de surfactante utilizadas.