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Microspheres Could Save Patients Whose Lungs Have Stopped Working

Doctors could eventually use the method to quickly reverse oxygen deprivation.

Researchers have developed a way to deliver oxygen to the body’s organs safely—via gas-filled microparticles—even when the patient’s lungs have stopped working. Doctors could one day use the method to quickly reverse oxygen deprivation in patients with acute loss of lung function while longer-term fixes such as heart-lung bypass support are put in place.

Air bubble: An intravenous infusion of oxygen-filled microparticles (the yellow sphere in this composite image) could carry the life-sustaining gas to red blood cells in patients with sudden loss of lung function.

Even short periods of oxygen deprivation put the vital organs of the body at risk. Typically, doctors feed oxygen-deprived patients the gas through ventilators such as tubes in the mouth or nose, but the treatment depends on functioning lungs. In situations where the airway is blocked or the lungs do not work, few options exist.

In such cases, injecting pure oxygen into the body is not an option because it can form bubbles in blood vessels and block blood flow. Some hospitals have machines that can oxygenate a patient’s blood outside of the body, but the surgical procedure to hook up such a bypass machine is complicated and can take too long in an emergency, says study author John Kheir.

As a first-year fellow at Boston Children’s Hospital a few years ago, Kheir treated a nine-month-old girl whose lungs had been damaged by pneumonia and were filled with blood. In the 20 or so minutes it took for Kheir and his colleagues to put her on the heart-lung bypass machine, she suffered severe brain injury from low oxygen levels and died. The experience led Kheir to work toward developing a fast-acting, intravenous treatment that could help patients like her with acute, severe lung injury. “The only way to save someone like that would be to inject oxygen directly into the vein,” he says. 

Blood substitutes that carry oxygen are available for transfusion, but are known to cause dangerous side effects and furthermore typically rely on functioning lungs. “There really is a need for something that you can pull off the shelf, and give to people to pull them through these critical periods,” says Ann Weinacker, a lung and critical care doctor at the Stanford Chest Clinic.

Kheir’s oxygen-filled microspheres, reported today in Science Translational Medicine, are around three micrometers in diameter and are diluted in a solution commonly used in transfusions so that the particles can flow through even small capillaries in the body. In test tubes, the researchers found the oxygen transferred from the microspheres to hemoglobin, the protein in red blood cells that carries oxygen, within four seconds. They then tested the microspheres in anesthetized rabbits with blocked windpipes. Although the rabbits were asphyxiated, their bodies were oxygenated and did not show signs of major injury to organs.

More research is necessary to determine how long the therapy can work and for how many patients it could be useful. “Situations where you have a short-term need [for oxygen] and everything else is working are not that common,” says Gail Weinmann, a lung disease expert with the National Heart Lung and Blood Institute. But when those situations arise, a quick infusion of oxygen could be life-saving, she says. “As a bridge, even 15 minutes could make a difference in some situations.”

Kheir says the intravenous oxygen delivery could help not only in the critical moments when heart-lung bypass machines are being set up, but also when patients are being put in intensive care on ventilators. Unstable patients with low lung function are also at risk of severely low oxygen levels, he says. “[The goal] is not to make ventilators obsolete, but to make patients healthier,” says Kheir.

Kheir says that more lab animal work is needed to explore the clinical utility of the microsphere technology, which he and some of the study coauthors are patenting. “We are testing the ability of these particles to deliver oxygen in other clinical circumstances, such as cardiac arrest and severe bleeding,” he says.

The team is also working on making the microspheres more stable, with the ultimate goal of creating an off-the-shelf solution that could be ready for quick use in emergency situations.

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