A Liquid Lifesaver for the Lungs
Before being born in August at Harbor-UCLA Medical Center, the fetus had a bowel movement in the womb that got into her lungs, producing chemical pneumonia. After delivery, physicians at Harbor-UCLA were unable to get enough oxygen into the infant’s blood and transferred her to Childrens Hospital Los Angeles, which has state-of-the-art technology for the management of lung disease.
None of the new technology worked, however, and Dr. Robert DeLemos decided to try a radical new approach that his team had previously used on only one other infant. They filled the little girl’s lungs with a chemical called perflubron that gently expanded the lungs’ small air sacs and transferred oxygen into her blood.
“The response was very dramatic,” DeLemos said. “Within eight hours, the baby’s measurements of oxygen in her blood had gone from a level that predicted she would die to a level which we knew meant she would recover.” Today, she is at home and doing well, he said.
Perflubron, a chemical cousin of the now ubiquitous Teflon, is exciting researchers throughout the country because of its ability to improve breathing in people with severe lung problems--a category that includes as many as 700,000 people each year, 150,000 of whom now die.
The treatment is useful for short-term respiratory distress caused by a broad range of traumas including pneumonia, inhalation of toxic substances, near drowning and smoke inhalation. It is not meant for people with long-term problems such as asthma.
Clinical trials are now in progress in adults, children and infants and the Food and Drug Administration has placed the treatment on the same fast track for approval occupied by the new AIDS drugs. New enthusiasm was sparked in September by a report in the New England Journal of Medicine that the use of perflubron in a technique called partial liquid ventilation saved the lives of seven of 10 premature infants who would in all likelihood have died otherwise.
“This is a very exciting new frontier in medicine that we have explored,” said Dr. Corinne Lowe Leach of Children’s Hospital of Buffalo, N.Y., one of the study’s authors. “It’s very exciting because babies who were not expected to survive did,” added physiologist Marla R. Wolfson of the Temple University School of Medicine in Philadelphia.
The new studies are the result of more than 30 years of experiments aimed at finding an artificial blood to supplement limited, fragile supplies of stored blood. Researchers have been looking at a class of chemicals called perfluorocarbons. These materials--composed almost entirely of carbon and fluorine, just like Teflon--do not appear to trigger any side effects because they do not chemically react with anything in the human body. They also carry relatively high amounts of needed oxygen, which is transferred into the bloodstream.
The ability of the fluids to support breathing was demonstrated in 1963 in a classic experiment by chemist Leland C. Clark Jr., now at Antioch College in Yellow Spring, Ohio. Clark attached a weight to the tail of a rat and submerged the animal in perfluorocarbon for several hours. The rat emerged unharmed.
Since then, many experiments have been performed to identify fluorochemicals that could carry enough oxygen, were compatible with tissues and were cleared from the body quickly. Perflubron (perfluorooctylbromide), which scored high in all these categories, was developed by Alliance Pharmaceutical Corp. of San Diego and trade-named LiquiVent. It is a clear, colorless, odorless, oily liquid that looks like water, but is twice as dense.
Proponents say the substance is a great improvement over the current way of treating patients with acute respiratory distress syndrome: a mechanical respirator, which inflates the lungs by forcing in air under pressure. But the alveoli--small air sacs--of infants’ lungs often stick together when they collapse during exhalation and cannot be reinflated. The relatively high pressures used to inflate the lungs can also rupture alveoli, causing bleeding and air leakage into the chest. And forced-air breathing does nothing to remove mucus, debris or water trapped in the alveoli.
Partial liquid ventilation, in contrast, gently expands the lungs and alveoli and holds them open. Perflubron, circulated through the lungs by a ventilator, also washes out liquids and debris, which are removed by a filter in the ventilator. “The goal . . . is to reduce the potential ill effects of conventional ventilator therapy so that physicians have more time to address the underlying causes of acute lung injury,” said Dr. Harry J. Kallas of UC Davis.
Waste carbon dioxide in the lungs also dissolves in the fluid and is removed by the ventilator. When therapy is complete, the perflubron is simply allowed to evaporate away.
Kallas’ first patient was a 10-year-old girl from the Central Valley who fell from a pickup truck into a muddy stream. When pulled from the water, she was not breathing and had no pulse.
CPR kept her alive until she reached the UC Davis Medical Center, where physicians suctioned muddy water from her lungs. The high ventilator pressures necessary to keep her oxygenated were damaging her lungs. Kallas filled her lungs with perflubron and kept them oxygenated for two days, which gave the lungs time to begin healing.
Within two weeks, the girl did not require any supplemental oxygen and was allowed to go home. Today, she is fully recovered.
One of the first success stories with the new treatment was Adrianna Mancini, who weighed 1 pound, 10 ounces when she was born three months prematurely in March 1994. The Philadelphia girl was baptized five hours after birth because her underdeveloped lungs made death appear inevitable.
But Dr. Jay Greenspan of Temple used partial liquid ventilation for three days to keep her alive until her lungs were better developed--the first time the fluid was used in an infant. Adrianna, now 2, is healthy and normal.
On her first birthday, she and her mother visited Alliance in San Diego to thank the researchers. Noted Gwen Rosenberg, director of corporate communications, “There wasn’t a dry eye in the company.”
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Breathing Easier
Liquid ventilation may be used tor escue a significant fraction of the 700,000 people who suffer from various forms of acute respiratoy distress syndrome each year. A fluorochemcial called perflubron, which dissolves large quantities of oxygen, is used to inflate the lungsand transfer oxygen into the blood stream.
* Running on empty: The lungs are made up of anetwork of tubes called bronchi, which feed oxygen to microsopic air sacs called alveoll. When these sacs collapse, no air can be stored or transferred into the blood.
* The way to reinflate: With the aid of a gas ventilator, the chemical perflubron is inhaled and fills the lungs where it works to expand collapsed air sacs, and transfer oxygen to the blood.
* Ventilator mixeds air with the perflubron liquid and forces it into the lungs.
Source: Alliance Pharmaceutical Corp.
