Effects of intravenous phosphodiesterase inhibitors and corticosteroids on severe meconium aspiration syndrome.

Abstract

Meconium aspiration syndrome (MAS) is a major cause of severe respiratory failure in near- and full-term neonates. Alleviating inflammation is key to successfully treating severe MAS. Phosphodiesterase (PDE) inhibitors are known to play a role in airway smooth muscle relaxation and alveolar inflammation inhibition. This study aimed to investigate the effects of various intravenous (IV) PDE inhibitors and corticosteroids on MAS. MAS was induced in newborn piglets by instilling human meconium in them. The piglets were randomly divided into five groups (n = 5 in each group): (1) control (sham treatment); (2) dexamethasone (Dex) (IV 0.6 mg/kg of dexamethasone); (3) aminophylline (Ami) (IV 6 mg/kg of aminophylline, followed by continuous infusion of 0.5 mg/kg/h of aminophylline; (4) milrinone (Mil) (IV 50 μg/kg of milrinone, followed by continuous infusion of 0.75 μg/kg/h of milrinone); and (5) rolipram (Rol) (IV 0.8 mg/kg of rolipram). The duration of the experimental period was 4 hours. Compared to the control group, all the four treatment groups revealed better oxygenation 3 hours and more after the start of treatment. The Rol group had a significantly elevated heart beat (p < 0.05) and relatively lower blood pressure compared to the other groups during the first 2 hours of the experiment. The Dex group had significantly lower interleukin (IL)-1β levels in the lung tissue compared to the other groups (p < 0.05) and significantly lower IL-6 levels compared to the Ami and Mil groups (p < 0.05). Lung histology showed slightly less inflammation and atelectasis in the Dex group compared to the other groups, but lung injury scores showed no significant between-group differences. Using IV corticosteroids or any type of PDE inhibitors has some beneficial effects in improving oxygenation in MAS. PDE inhibitors are not superior to IV corticosteroids; in fact, adverse cardiovascular effects occur with the phosphodiesterase type 4 (PDE4) inhibitor. Further investigations are required before using IV corticosteroids and PDE inhibitors in future clinical application.