Heart Murmurs

Summer 2013

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Intravenous oxygen delivery

Bridging the gap between academic research and clinical need

John Kheir Boston Children's

Over the years that Boston Children’s Hospital’s John Kheir, MD, has been developing intravenous oxygen delivery, he’s faced frustrating setbacks, reached exciting milestones and encountered a few surprises. What’s surprised him the most, he says, is that “a lot of engi­neers work on things because of purely academic interest and not because of a clinical need.” Many institutions “work in a bubble,” he states, creating a “real disconnect between the science that’s available and the needs of patients.”

For Kheir, addressing that discon­nect has been his life’s work since 2006. That year, Kheir and his colleagues were caring for a young girl named Jordan who suffered a severe brain injury, a result of pneumonia that caused bleeding into her lungs. Unfortunately, Jordan’s blood oxygen level dropped so low and so quickly that even though her care team immediately put her on a heart-lung machine, she died a few days later.

That experience inspired Kheir to search for a new way to get oxygen into the blood. Initially, he drew on work done in the 1970s and 1980s in which gas-filled microparticles were created to address certain conditions. “Typically,” he explains, “those particles were surround­ed by a lipid shell, usually filled with insoluble gasses that stabilize the lipid particle... We knew that we had to make a small particle that was coated with something that could work.”

After much trial and error, Kheir and his colleagues created a microparticle made up of a pocket of oxygen gas sur­rounded by a single layer of lipids. Last year, in a paper published in Science Translational Medicine, they reported on successful experiments in which this microparticle was injected into animals with low blood oxygen levels. The paper described how intravenous oxygen delivery quickly restored their blood oxygen to near-normal levels.

Portable and fast-acting, Kheir’s injectable solution could help stabilize patients in emergency situations—sit­uations like the one Jordan faced in 2006. “This project is unique in that it was completely inspired by a patient experience,” Kheir asserts, emphasizing the clear clinical focus that guided his research.

Looking back on his work, Kheir says that he was “surprised by how difficult it is to make something new... Every piece of equipment, every measurement, every amount of chemical, every subtle nuance to an experiment matters. You cannot do good science without exqui­site attention to detail,” he explains.

Also, he says, you cannot do quality research without removing the “discon­nect” between researchers and clinicians and forging collaborations between departments and disciplines. “One of the great advantages of working in a large institution like BCH is that the needs and skills necessary for a project like this can be put together in the same place,” he says.

Kheir says he’s received invaluable assistance from medical doctors, sci­entists, engineers and technicians from throughout Boston Children’s. Much-needed help has also come from the hospi­tal’s Technology & Innovation Development Office (TIDO). TIDO, he says, has provided necessary funding, and “we’ve filed six patents together. It’s been a great collaboration.”

   
 Nitrogen gas deoxygenates donated blood, mimicking human blood when airways are blocked.
 Billions of tiny gas-filed microparticles appear as a fluffy white powder when collected.

Work on oxygenation continues. Kheir says his team has completed several proof-of-concept studies and is now addressing questions that must be answered before intravenous oxygen delivery can move from the laboratory to the clinic. These questions center on finding the optimum storage capacity for the microparticle and determining the appropriate timing for injecting oxygen into a patient.

When will injectable oxygen be ready for real-world use? Kheir can’t say for sure, but “every time we de-risk something and move closer, I get more optimistic that it will on a three-to-five-year timetable,” he says.

“But,” Kheir states, “close isn’t done. Close is close.” And, he adds, “Until we have something in our hands that we’re sure will work, I can’t say when it will be ready.”

But one thing he can say for sure is that bridging the gap between clinical necessity and academic interest has brought his work this far—and that’s a long way.

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