When a critically ill neonate or infant has severe refractory pulmonary hypertension (PH), they are given the maximum possible therapies to restore their cardiorespiratory function while in the neonatal intensive care unit (NICU). But even with a “kitchen sink” strategy, many of these infants do not survive.
Usha Krishnan, MD, a pediatric cardiologist and director of the Pulmonary Hypertension Comprehensive Care Center at New York-Presbyterian and Columbia, recently studied the use of continuous inhaled iloprost as a rescue therapy for neonates and infants with refractory PH. Below, she discusses findings from her recent study describing New York-Presbyterian and Columbia’s experience using continuous inhaled iloprost in extremely ill NICU patients with severe pulmonary hypertensive crises.
New York-Presbyterian and Columbia is one of few centers in the country that uses iloprost as a continuous inhaled therapy for neonates and infants.
— Dr. Usha Krishnan
Use of Continuous Inhaled Iloprost
Neonates and infants in the NICU with Pulmonary Hypertension are very sick and if not appropriately treated in a timely manner, their outcomes could be a relentless spiral towards death. In infants with PH crises despite maximal inhaled nitric oxide and inotropes, we use continuous inhaled iloprost as a last-resort option prior to canulation for ECMO. Intravenous prostanoids which have been used in refractory PH require a central line, which often cannot be placed in critically ill neonates and infants. There may also be systemic hypotension as well as ventilation –perfusion mismatch with intravenous or subcutaneous use of prostanoids. By delivering medication directly to the patients’ lungs, we were able to have the medication reach its target organ without causing significant systemic side effects and mismatch.
Our study is the largest analysis to date of continuous inhaled iloprost in the NICU. New York-Presbyterian and Columbia is one of few centers in the country that uses iloprost as a continuous inhaled therapy for neonates and infants. In adults, it is typically given every three to four hours; however, by providing the medication continuously, we hoped to prevent them from declining further due to ups and downs in the medication levels and resultant swings in the level of PH.
Safety and Tolerability
In our study, we reviewed the charts of 51 patients in two age groups - 32 neonates who were under 4 weeks of age and 19 infants between 4 weeks to 1 year of age — who were treated with continuous inhaled iloprost for at least six hours.
Using continuous inhaled iloprost in the NICU needs to be a team effort, as it should only be used under the guidance of a pulmonary hypertension specialist and a neonatologist.
— Dr. Usha Krishnan
Overall, infants in both age groups tolerated continuous inhaled iloprost well. The medication safely decreased the infants’ fraction of inspired oxygen and oxygenation index; there was no negative impact on their mean airway pressures, blood pressures, or heart rates. Additionally, there were no significant differences in tolerance between the neonate group and the infant group.
Using continuous inhaled iloprost in the NICU needs to be a team effort, as it should only be used under the guidance of a pulmonary hypertension specialist and a neonatologist. At New York-Presbyterian and Columbia, we have one of the largest PH programs of its kind in the country. We have a multidisciplinary team approach to manage the sickest infants in the NICU including those with PPHN, bronchopulmonary dysplasia and congenital diaphragmatic hernia, in addition to having a dedicated neonatal cardiac ICU.
Study Results
While 24 of the 51 (47%) patients recovered without requiring extracorporeal membrane oxygenation (ECMO), there were 12 (23%) patients who died. There were 15 patients in this study who were placed on ECMO. Of these 15 patients, 7 were bridged off ECMO using continuous inhaled iloprost, and 8 died.
Continuous inhaled iloprost can help patients who may be put on ECMO in multiple ways: in some cases, it can stabilize them so that ECMO is no longer necessary. For patients who still require ECMO after being treated with continuous inhaled iloprost, it can help them better tolerate going onto and while bridging off of ECMO.
Future Implications
Though iloprost is not a new medication, its use as a continuous inhaled therapy in critically ill babies in the NICU may help improve outcomes. At this time, New York-Presbyterian and Columbia is the only PH center in the tri-state area that uses continuously inhaled iloprost to treat infants.
Continuous inhaled iloprost is a valuable addition to the armamentarium of medications for refractory PH in infants.
— Dr. Usha Krishnan
Having another tool in the toolbox, especially one that is inhaled, is crucial for managing PH in the NICU. While it should always be used with caution and is contraindicated in patients with Group 2 PH- those with pulmonary veins stenosis or congenital heart lesions involving obstructions or poor function of the left side of the heart.
To conclude, continuous inhaled iloprost is a valuable addition to the armamentarium of medications for refractory PH in infants. Of note, most of these medications used in this age group are used off-label and should only be used by experienced practitioners in the field.
