Prostaglandin E1 an effective add-on for PH in newborns, study finds
Muscle relaxant seen to aid heart in pumping blood, improving oxygen flow
Babies with persistent pulmonary hypertension of the newborn (PPHN) started quickly on treatment with prostaglandin E1 (PGE1) — which lowers blood pressure by allowing blood vessels to relax and open up — show a better working heart and a lesser need of extra oxygen, a study reports.
“Importantly, the use of PGE in these severely ill infants was beneficial without clinically significant side effects or impaired oxygenation,” the researchers wrote, urging further investigations into its use.
The study, “Prostaglandin-E1 infusion in persistent pulmonary hypertension of the newborn,” was published in the journal Pediatric Pulmonology by a team of scientists with the University of California San Francisco.
Persistent pulmonary hypertension of the newborn is rare, serious disease
Before birth, a baby’s lungs are filled with amniotic fluid, the fluid that surrounds and protects the child in the womb. Circulating blood is diverted from the lungs by flowing through a special ductus or passageway.
When the baby is born and begins breathing, the ductus closes. The amniotic fluid is cleared and pressure in the lungs falls, allowing blood to travel into them. In babies with PPHN, however, pressure in the lungs stays high.
As a result, the heart’s right ventricle (bottom chamber) needs to work harder to pump the blood out to the lungs, weakening the heart and causing the blood to shunt from the right to the left side of the heart.
While a main goal of disease treatment is to increase oxygen flow to the baby’s organs to prevent serious complications, “limited literature suggests optimal management strategies,” the researchers wrote.
They reviewed the medical records of 57 babies with PPHN who were born at their university’s Benioff Children’s Hospital from 2015 to 2020 and treated with PGE1 to keep the ductus open or to reopen it.
In the U.S., PGE1 can be used to help the ductus stay open temporarily in babies with a congenital (present at birth) heart disease that blocks blood flow to the lungs. PGE1 allows the blood to pick up enough oxygen until surgery is possible to correct the heart defect.
Infusion of PGE1 was used to keep the ductus open in 34 (60%) babies and to reopen it in 19 (33%). Four (7%) newborns did not have an echocardiogram (an ultrasound test that checks the structure of the heart) available to check the status of the ductus.
Most babies (95%) were treated with inhaled nitric oxide — to relax and widen blood vessels — and 16 (28%) received extracorporeal membrane oxygenation for an average of 5.8 days, oxygenating the blood in an external heart-lung machine. All received breathing support, most (95%) with invasive mechanical ventilation.
PGE1 typically started within 2 days of birth, and given for several days
PGE1 was started a mean of 1.3 days after birth at an infused dose ranging from 0.0125 to 0.1 micrograms per kilogram of body weight per minute. Treatment was continued for about six days and stopped when these newborns were a mean of 6.4 days old.
Within 24 hours of treatment, heart rate decreased significantly by a mean 10.3 heartbeats per minute. Blood lactate, a marker of low oxygen levels in tissues, also fall by a significant 1.8 millimoles per liter.
Oxygen saturation index, where a higher score indicates more severe lung disease, also decreased significantly by eight points, suggesting the need for less supplemental oxygen.
PGE1 was started a mean of 2.1 days earlier in babies needing it to keep the ductus open than in those where it was used to reopen the ductus (0.6 vs. 2.7 days). An earlier normalization of blood lactate levels (1.3 vs. 4.1 days) also was seen in these infants.
After treatment, fractional area change, a measure of systolic function (how well the heart pumps), increased significantly. Pulmonary arterial acceleration time indexed to right ventricular ejection time, a measure of the heart’s right ventricle performance, also improved.
The use of PGE1 “appears to be a safe and useful adjunctive [add-on] therapy to promote the natural resolution of PPHN in the setting of severe disease,” the researchers wrote.
While PGE1 led to better “cardiac output and preserved [right ventricular] systolic function without impaired oxygenation,” the team added, more studies are needed to determine who may benefit the most from treatment, when is the best time to start, and how long should it continue.