Inhaled Prostaglandin E1 for Treatment of Acute Lung Injury in Severe Multiple Organ Failure

Abstract

In patients with severe acute lung injury and multiple organ failure, inhaled prostaglandin E1 improved oxygenation and decreased venous admixture without affecting systemic hemodynamic variables. Controlled clinical trials are warranted.

Aerosol Delivery in Ventilated Newborn Pigs: An MRI Evaluation

“…However, lack of sustained improvement in 30 -46% of infants and the need for specialized delivery systems make the treatment expensive and limit availability. Several investigators have explored the use of aerosolized prostaglandin E 1 (PGE 1 ) as a selective pulmonary vasodilator in patients with respiratory failure to improve oxygenation because of its selective action not only on the pulmonary circulation, but also on well-ventilated lung units (2)(3)(4)(5). We have previously described the safety and feasibility of inhaled PGE 1 (IPGE 1 ) in NHRF in a phase I/II unblinded clinical trial (5).…”

Toxicity of prolonged high dose inhaled PGE1 in ventilated neonatal pigs

“…In an in vitro study, we have demonstrated that the emitted dose of IPGE 1 following jet nebulization in a neonatal ventilator circuit was 32-40% (26). In the present study, we used a high dose of IPGE 1 , 1200 ng/kg/min, corresponding to a total dose of ~3,500 μg of PGE 1 administered over 24 h. Compared to doses known to reduce pulmonary hypertension in patients (8-300 ng/kg/min), this represents a high dose (7)(8)(9)20,28,36). A dose of 1200 ng/ kg/min was chosen as this represents a dose four times the maximal dose that has been reported in humans and when given over a 24-hour period represents the cumulative dose that would be delivered over several days in the clinically used doses.…”

“…Intravenous PGE 1 (ivPGE 1 ) and PGI 2 , potent vasodilators used empirically in the treatment of NHRF, are associated with systemic hypotension and worsening of oxygenation due to increased venous admixture (2)(3)(4)(5)(6). This has led investigators to explore the delivery of PGE 1 and PGI 2 directly to the lungs as an inhalation, thus minimizing systemic effects and achieving selective pulmonary vasodilation (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21). Compared to PGI 2 , PGE 1 has a shorter half-life, lower pH (6.3 versus 10.5), bronchodilator action, anti-proliferative and anti-inflammatory effects on the alveolar, interstitial and vascular spaces of the lung (8,(22)(23)(24)(25).…”

“…This has led investigators to explore the delivery of PGE 1 and PGI 2 directly to the lungs as an inhalation, thus minimizing systemic effects and achieving selective pulmonary vasodilation (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21). Compared to PGI 2 , PGE 1 has a shorter half-life, lower pH (6.3 versus 10.5), bronchodilator action, anti-proliferative and anti-inflammatory effects on the alveolar, interstitial and vascular spaces of the lung (8,(22)(23)(24)(25). We have described the emitted dose, stability and aerosol particle size distribution of inhaled PGE 1 in a neonatal ventilator circuit and demonstrated effective pulmonary delivery using magnetic resonance imaging in a ventilated piglet model (26,27).…”

Aerosolized PGE1: A Selective Pulmonary Vasodilator in Neonatal Hypoxemic Respiratory Failure Results of a Phase I/II Open Label Clinical Trial

“…However, there is lack of sustained improvement in 30 -46% of infants (1)(2)(3)(4); moreover, INO is a highly toxic molecule requiring expensive monitoring and scavenging systems for administration, making the treatment expensive and limiting availability. Aerosolized prostaglandins I 2 and E 1 have been reported to be effective selective pulmonary vasodilators in animals and human adults (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19). In addition, inhaled PGI 2 (IPGI 2 ) has also been reported to be effective in preterm and term newborns and children with pulmonary hypertension (20 -26).…”