Pharmacotherapy for meconium aspiration

Meconium aspiration syndrome (MAS) is defined as the presence of respiratory distress and hypoxemia associated with the presence of meconium during or just before delivery. This condition requires, in the most severe cases, assisted ventilation for more than 48 h and is often associated with pulmonary hypertension.
The treatment options for moderate-to-severe MAS can be divided into general or specific. The general treatment options are represented by the optimization of ventilation, sedation and alkalanization. On the other hand, the more specific pharmacological therapies are aimed at reducing hypoxia with the use of pulmonary vasodilators, such as inhaled nitric oxide, oral sildenafil and bosentan, and the lung injury by anti-inflammatory agents, surfactant lavage or replacement.
For what concerns general management, in all newborns with evidence of severe respiratory distress handling is minimized to prevent worsening of gas exchange due to agitation. Moreover, sedation and analgesia are frequently used to alleviate pain and discomfort that may lead to hypoxia and right-to-left shunting. Opioids are frequently used across the world, but major side effects of these medications and lack of information on their long-term impact limit their utilization. Similar concerns can be noted for muscle relaxants: in particular, neonatologists are urged to consider the risks and benefits of neuromuscular blockade prior to their use.
Alkalinization either by hyperventilation or by sodium bicarbonate infusion is another common strategy for the management of MAS. However, both strategies should be used with caution due to their adverse effects on cerebral and coronary circulation.
MAS is frequently associated to pulmonary hypertension secondary to hypoxia, acidosis, release of the inflammatory mediators and alveolar atelectasis. This condition should ideally be treated with adequate ventilation and pulmonary vasodilators. In particular, inhaled nitric oxide (INO) may represent an ideal pulmonary vasodilator since it has been shown to decrease pulmonary vascular resistance but not systemic vascular resistance and to rapidly relieve hypoxia, acidosis and vasoconstriction. Moreover, it has no or minimal systemic effects and is rapidly metabolized and cleared. Phosphodiesterase (PDE) inhibitors are another class of drugs used in the treatment of pulmonary hypertension. In particular, sildenafil, the most specific PDE-5 inhibitor currently available, it is becoming increasingly popular, but a large multicenter study is needed to assess its safety and efficacy with or without INO. Bosentan, an endothelin antagonist approved by the FDA for the treatment of pulmonary hypertension in adults, may represent another option, but in pediatric and neonatal populations information is limited to case reports. At present, other newer pulmonary vasodilators, like superoxide dismutase, vasoactive intestinal peptide, adrenomedulline and arginine, are being developed.
Other therapeutic strategies are now being evaluated for the protection of lung damage. For instance, surfactant administration represents a promising therapy. In fact, meconium contents are highly viscous and consist of desquamated epithelial cells and thickened intestinal secretions; moreover, glycoproteins of meconium cause increased adhesiveness. Of note, meconium constituents, especially fatty acids, other soluble proteins and bilirubin are direct inhibitors of surfactant. The efficacy of surfactant administration was evaluated in two randomized control studies, which reported significant improvement in oxygenation and decrease in barotrauma with surfactant treatment.

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