Study Shows Partial Liquid Breathing Improves Lung Function In Desperately Ill Preemies

SAN DIEGO -- An experimental treatment for life-threatening respiratory distress syndrome, developed by researchers at the University at Buffalo and Children's Hospital of Buffalo, is safe and can save the lives of seriously ill premature infants, results of a five-center pilot study have shown.

The procedure, called partial liquid ventilation (PLV), is a type of liquid breathing that sounds more like science fiction than fact.

The results of the first human trial of PLV showed that lung functioning improved markedly in 11 of 13 premature infants who had failed to respond to conventional therapy.

Corinne L. Leach, M.D., Ph.D., UB assistant professor of pediatrics and principal investigator on the pilot study, reported the results today at a meeting of the Society for Pediatric Research.

The life-support technique involves introducing a chemical substance called perflubron -- a colorless, odorless, chemically inert liquid that contains no water, but possesses a strong affinity for oxygen -- through the trachea and into the patient's stiff, malfunctioning lungs. A standard ventilator pumps oxygen into the liquid in measured bursts. The liquid allows the lungs to inflate with less pressure than air, and permits oxygen and carbon dioxide to pass through the alveoli, or air sacs, more easily and efficiently.

PLV was developed by Bradley Fuhrman, M.D., UB professor of pediatrics and chief of pediatric critical care at Children's Hospital. The procedure is a modification of total liquid breathing, a technique pioneered by Thomas Shaffer, Ph.D., of Temple University.

Respiratory distress syndrome develops in many premature infants because their lungs have yet to secrete surfactant, the substance that prevents the air sacs from collapsing. It is the leading cause of death in these babies. Earlier studies conducted by Leach and others had shown that PLV could improve gas exchange and lung functioning in animal models of respiratory distress syndrome.

Conventional ventilation therapy for respiratory distress syndrome -- increasing air pressure and oxygen concentration inside the lung in an effort to force more oxygen into the bloodstream -- can cause permanent lung injury and result in a chronic disease called bronchopulmonary dysplasia.

"The successful introduction of liquid into the lung and the ability of infants to breathe with liquid allows us to ventilate the lung at lower pressure, which generates less damage," Leach said. "If we can decrease the amount of lung injury, we can greatly improve the patients' outcome, and perhaps prevent chronic lung disease."

The pilot study involved 13 infants born between 24-34 weeks of gestation. All had failed to respond to conventional therapy -- which included receiving at least two doses of surfactant and maximized conventional ventilator support -- and had blood-gas levels indicating severe respiratory distress, and were at risk of dying.

Perflubron was instilled through a tube in the trachea, and oxygen was introduced into the liquid using a standard ventilator. The infants remained on PLV for periods ranging from one hour to three days.

Results showed that placing the infants on liquid ventilation caused no serious negative side effects. Temperature, heart rate and blood pressure were not affected.

Carbon-dioxide levels improved in all patients while on PLV and lung functioning improved in 11 infants. Other measures of respiratory functioning -- oxygenation index, dynamic compliance and mean airway pressure -- also improved.

Seven of the 13 critically ill infants survived. Of those who died, three succumbed to their acute lung disease, and one from bronchopulmonary dysplasia. Two patients died of non-respiratory complications of prematurity.

Leach said the pilot study shows that PLV may be an effective treatment option for very premature babies who have not responded to conventional therapy for respiratory distress syndrome.

Clinical pilot studies using PLV to treat children and adults with severe respiratory distress syndrome also are under way and results are promising, Leach said.

Additional centers participating in the PLV study with premature newborns are Jefferson Medical Center, Temple University School of Medicine/St. Christopher's Hospital for Children in Philadelphia, University of Washington and the University of Southern California Medical Center.

The pilot study was sponsored by Alliance Pharmaceutical Corporation, San Diego, Calif., manufacturer of the perflubron LiquiVent™, and was conducted under a new-drug application with the U.S. Food and Drug Administration.