Premature Babies Benefit From Inhaling Nitric Oxide At Shands At The University Of Florida

Shands Public Relations

GAINESVILLE, Fla.---A gas commonly found in smog and cigarette smoke actually helps premature babies by opening blood vessels in their underdeveloped lungs, causing blood oxygen levels to rise, University of Florida researchers report. Though researchers have not yet put nitric oxide to the kind of rigorous scientific scrutiny that would allow them to declare the gas saves lives, early indications point to a significant improvement in the health of the sickest pre-term infants.

UF physicians administered the gas through mechanical ventilators to 23 preterm infants diagnosed with respiratory distress syndrome, they reported in the February issue of Journal of Pediatrics. The babies, undergoing treatment in the Neonatal Intensive Care Unit at Shands at UF, were between 27 and 35 weeks' gestation and weighed an average of 2.5 pounds, as light as a dozen boxes of paper clips.

The babies were randomly assigned to receive low concentrations of nitric oxide for 15 minutes and were studied one to seven days after delivery. Pre-term infants typically have underdeveloped, partially collapsed lungs that cannot absorb oxygen as well as normal ones. Pre-term infants may therefore die or suffer from long-term complications caused by low levels of oxygen in their blood. Nitric oxide improves the uptake of oxygen so it can get to the brain and other vital organs, says pediatric cardiologist Dr. Jeffrey W. Skimming, an assistant professor at UF's College of Medicine and the study's principal investigator.

"Nitric oxide opens blood vessels. Because this drug is inhaled, it passes into healthy lung regions and bypasses those that have blocked air passages. Blood is thereby re-routed toward the healthy regions," Skimming said. "We believe that this re-routing of blood causes oxygen levels in the blood to rise."

The study was not designed to determine the toxic effects of nitric oxide or whether use of the gas improves survival. But because they noted such significant increases in blood oxygen levels, physicians say additional studies should be performed to better evaluate nitric oxide's therapeutic potential. Dr. Willa Drummond, a UF neonatologist and the paper's co-author, said nitric oxide is particularly useful for critically ill babies who are too small to be treated with conventional means of raising blood oxygen levels. Drummond witnessed the gas' benefits firsthand when she treated a baby girl born 10 weeks early on Jan. 5. On Feb. 21, the baby was discharged from the hospital with no obvious complications.

"To be able to let that baby go home without any chronic lung or brain disease in only seven weeks is really a miracle, considering how sick she was," Drummond said. "We all thought she was not going to survive." The Food and Drug Administration recently deemed nitric oxide an experimental drug. Since 1993, UF physicians have used it to treat more than 400 patients -- from premature infants to children and adults with various lung diseases.

"Unlike antibiotics or other drugs that directly attack specific diseases, nitric oxide treatment may simply help keep the most critically ill patients alive so that both development and healing can occur naturally," Skimming said.

The federal Occupational Safety and Health Administration has set limits for safe exposure to nitric oxide in the workplace at about 25 parts per million. The infants in the UF study received either 5 or 20 parts per million. In contrast, a smoker inhales about 1,000 parts per million with each cigarette, while ambient air concentrations of nitric oxide around a city such as Los Angeles register about one-twentieth of a part per million, Skimming estimated.

"Many people studied the toxicity of this drug, long before they recognized it had therapeutic value," Skimming said. "Balancing the toxic aspects with the therapeutic aspects of our interventions is a necessary art in medicine." Nitric oxide is not the only substance with such paradoxical qualities. "Oxygen can be a poison if it is inhaled in its pure form for a prolonged period of time -- it can kill you," she said. "Both nitric oxide and oxygen have similar types of toxicity and biochemical effects."

Nevertheless, it's not surprising the journal Science declared nitric oxide the 1992 Molecule of the Year.

"These findings could have profound ramifications. What are the biggest killers worldwide? Heart attacks? Stroke? Cancer? It depends on your perception of life," Skimming said. "If you don't think of pre-term infants as being viable people, then you should accept those answers. If you think differently, then you should believe that prematurity is the biggest killer on a worldwide basis -- some studies report that over 30 percent of all births worldwide result in death from prematurity.