No Lungs Required: Injected Oxygen to Keep Patients Alive

Because of pneumonia, the patient?s lungs were filling with blood. There was only one option to save the little girl, and so the team including cardiologist John Kheir?who was in training at the time, in 2006?raced to get her hooked up to a heart?lung machine, an external device that oxygenates and pumps blood around the body. But connecting a patient to the machine takes time, and the girl?s blood oxygen levels were dropping fast. She suffered severe brain damage and died before the team could even connect her to the machine. "I was pretty frustrated that we were unable to support her oxygen delivery, even though she was already in intensive care," Kheir tells PM. But that frustration was the germ of a potential breakthrough: "I thought that maybe we could get rid of the need for the lungs to provide oxygen, by injecting it into the bloodstream."

Beginning in World War I, doctors attempted to inject oxygen gas straight into patients? bloodstreams, but to no avail. Instead of raising the patients? blood oxygen levels, the gas gathered in air bubbles that fatally blocked blood flow. But this week, in a paper published in Science Translational Medicine, Kheir and his colleagues at the Boston Children?s Hospital say they have found a way to package oxygen inside of microscopic shells. Once injected, the flexible coatings can pass the oxygen directly to the red blood cells before the gas has a chance to form bubbles. The oxygen microparticles may one day allow doctors to safely inject oxygen directly into patients who can?t breathe through their nose or mouth.

The oxygen microparticles haven?t been tested on humans yet, so it would be years before they entered the ER. But "the notion that one could have an intravenous agent to deliver oxygen to the bloodstream, without gas bubbles, is pretty exciting work," says David Wessel, a critical care specialist at Children?s National Medical Center in Washington, D.C. When a patient suffers a blocked airway or damaged lungs, "the measures to try to establish an airway can be pretty extreme," Wessel says. Doctors may have to cut a small hole through the neck and windpipe (in a procedure called a tracheostomy), or put the patient into a heart?lung machine, which can be labor intensive and high risk. Without oxygen, the body may go into cardiac arrest or suffer brain damage.

A Few Minutes More

The researchers started by creating tiny (4-micrometer-wide) air bubbles by filling a chamber with oxygen, a kind of molecule called phospholipids, and a fluid similar to blood plasma. They fired sound waves at the chamber so that the gas and fluids would mix. During that process, the fatty phospholipids encircled the oxygen gas?similarly to the bubbles that form when you shake up a bottle of oil and water mixture?and the phospholipid shells hold the oxygen in suspension. When mixed with blood, the oily bubbles readily give up their oxygen to the hungry red blood cells. "The chemistry basically does all the work," Kheir says.

In a preliminary experiment, the researchers anesthetized rabbits and gave them a paralyzing medication so that they could not breathe on their own. They cut off each rabbit?s air supply for 15 minutes. Seven rabbits received injections of the oxygen microparticles, which kept their blood oxygen levels above the danger zone. Rabbits in this group fared well. But the control group didn?t receive oxygen of any kind; all six suffered cardiac arrest and organ failure.

Notably, though, one rabbit injected with the oxygen microparticles suffered cardiac arrest, apparently because of a buildup of carbon dioxide. That?s the concern with these particles, according to Warren Zapol, an anesthesiologist at Massachusetts General Hospital who doubts their practicality: If an animal is unable to exhale CO2, the gas fuses with water in the blood to form carbonic acid, which can lead to organ failure. "Obviously [this treatment] doesn?t remove carbon dioxide so it?s only doing half the job," he says. "You can live with your carbon dioxide going up, but you won?t be a happy person. Can you buy a few minutes with this? Maybe."

Stephen Trzeciak, an emergency medicine and critical care specialist at Cooper University Hospital in New Jersey, disagrees. "I don?t see carbon dioxide as even being an issue. Having a high carbon dioxide level isn?t what kills people. It?s the lack of oxygen."

It?s true that the oxygen microparticles would not sustain a person indefinitely. "I think it?s conceivable that [the treatment] could keep someone alive for 20 or 30 minutes," Kheir says. But in the emergency room, Trzeciak says, even a few extra minutes can be a precious resource. "You could infuse the oxygen intravenously, to get enough oxygen into the blood while you get a definitive fix on whatever is wrong." He says that the treatment could keep oxygen levels stable while doctors perform a tracheostomy or hook the patient up to a heart-lung machine?perhaps providing the stopgap solution that Kheir needed back in 2006.

Scaling Up

Because humans are much larger than rabbits, keeping a person?s blood oxygen levels up during an emergency would require injecting much larger volumes of the oxygen microparticles continuously. Kheir estimates that to keep an adult alive for ten minutes, doctors would need to inject 2 liters of oxygen microparticles into the patient?s body. Imagine trying to empty a 2-liter soda bottle into your blood stream in just a few minutes.

Fortunately, he says, your hemoglobin picks up oxygen quickly and the empty phospholipid shell collapses, so the actual volume added to the bloodstream is closer to 600 or 700 milliliters. Kheir would like to decrease that volume even more by increasing the concentration of microparticles, but the team has its work cut out. Although Kheir and colleagues managed to create a substance that contained 90 percent oxygen microparticles and only 10 percent fluid, the substance had the consistency of shaving cream and couldn?t be injected effectively. The mixture that they tested in rabbits was closer to 65 percent oxygen.

The team also must determine any long-term risks of the treatment, and figure out how the body breaks down the phospholipids shell once it releases its oxygen, before a drug like this makes it to the hospital. "There?s a lot of obstacles that would have to be dealt with," Wessel says, "but this represents a very novel idea with potentially enormous benefits."

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