Administration of Inhaled Pulmonary Vasodilators to the Mechanically Ventilated Neonatal Patient

Abstract

Pulmonary hypertension is a life-threatening condition that affects people of all ages that can occur as an idiopathic disorder at birth or as part of a variety of cardiovascular and infectious disorders. It is commonly treated with inhaled pulmonary vasodilators such as nitric oxide and less frequently using formulations and analogs of prostacyclin. To minimize systemic effects and preserve pulmonary vasodilation, vasodilators are often administered directly into the airway. Nitric oxide is the only USA Food and Drug Administration-approved inhaled pulmonary vasodilator that can be used during mechanical ventilation. Over the past two decades, interest has grown in the use of aerosolized prostacyclin and prostacyclin analogs for the treatment of pulmonary hypertension during mechanical ventilation. Clinicians who administer inhaled prostacyclin may not have a clear understanding of its risks because of the lack of data from large clinical trials examining safety and efficacy; moreover, its safe use remains poorly documented. The off-label use of drugs is legitimate, but prescribers must recognize the potential complications and liability in doing so. This manuscript aims to address potential problems related to the aerosol administration of pulmonary vasodilators in the mechanically ventilated neonatal patient.

Nebulized Magnesium Sulfate for Treatment of Persistent Pulmonary Hypertension of Newborn: A Pilot Randomized Controlled Trial

“…Scintigraphic studies demonstrate that the amount of nebulized drug that reaches alveolar space during mechanical ventilation is < 10%-20% of the volume placed in the reservoir of nebulizer; this may be even lower in neonates with relatively larger dead spaces and those not connected to mechanical ventilation. Therefore, nebulized magnesium sulfate may have limited effectiveness in spontaneously breathing neonates with mild PPHN [23][24][25]. Delivery of nebulized drugs during mechanical ventilation is technically complex and affected by numerous variables related to solution properties, nebulizer, humidification and heating systems, breathing circuit and artificial airways, ventilator settings, patient, and lung anatomy and pathology [17,23,25,26].…”

“…Therefore, nebulized magnesium sulfate may have limited effectiveness in spontaneously breathing neonates with mild PPHN [23][24][25]. Delivery of nebulized drugs during mechanical ventilation is technically complex and affected by numerous variables related to solution properties, nebulizer, humidification and heating systems, breathing circuit and artificial airways, ventilator settings, patient, and lung anatomy and pathology [17,23,25,26]. Having an efficient and consistent nebulization system during mechanical ventilation remains technically challenging.…”

A Treatment to Eliminate SARS-CoV-2 Replication in Human Airway Epithelial Cells Is Safe for Inhalation as an Aerosol in Healthy Human Subjects

“…Inhalation of pH-altering compounds should be done with caution. Exposures to pH above 10 and below 6.5 are known to adversely effect NHAE cell function 7,22 .…”

“…ALF acidification contributes to the pathophysiology of asthma and other respiratory diseases [1][2][3] . Specifically, ALF acidification is known to increase cough and bronchospasm, facilitate bacterial growth, increase mucus viscosity, decrease ciliary beat frequency, and cause general epithelial dysfunction 2,[4][5][6][7][8][9][10] . ALF acidification occurs during inflammatory and infectious airway disease exacerbations 2,6,[8][9][10][11][12] .…”

Inhaled Pulmonary Vasodilators in the Neonatal and Pediatric ICU

“…89 Treprostinil. Treprostinil is a prostacyclin analog similar to iloprost and is chemically stable with a much longer halflife, 95 which leads to a more favorable and less labor-intensive administration schedule. 99 However, the data on inhaled treprostinil are very limited.…”