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

J Chin Med Assoc. 2019 Jul;82(7):568-575. doi: 10.1097/JCMA.0000000000000063.

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

MeSH terms

  • Administration, Intravenous
  • Adrenal Cortex Hormones / therapeutic use*
  • Animals
  • C-Reactive Protein / analysis
  • Humans
  • Interleukin-1beta / blood
  • Interleukin-6 / blood
  • Meconium Aspiration Syndrome / drug therapy*
  • Meconium Aspiration Syndrome / immunology
  • Meconium Aspiration Syndrome / physiopathology
  • Oxygen / blood
  • Phosphodiesterase Inhibitors / therapeutic use*
  • Swine

Substances

  • Adrenal Cortex Hormones
  • IL6 protein, human
  • Interleukin-1beta
  • Interleukin-6
  • Phosphodiesterase Inhibitors
  • C-Reactive Protein
  • Oxygen