Challenging ICU event inspires investigator to create injectable oxygen

Oxygen microparticles could buy time in urgent situations when breathing is impaired

John Kheir oxygen mictoparticle

Patients unable to breathe because of acute lung failure or an obstructed airway need another way to get oxygen into their blood – fast – to avoid cardiac arrest and brain injury. Extending that oxygenation of the blood by minutes can mean the difference between life and death—a situation Dr. John Kheir, MD, staff physician and researcher in the Cardiac Intensive Care Unit at Boston Children’s, experienced for himself. And it is this experience that led to his idea and passion to use oxygenated microparticle injections to keep patients alive in the future when time is critical.

Here, Dr. Kheir describes his moment of inspiration and path to discovery.

“One of my patients was a 9-month-old girl who was admitted with pneumonia, and was having trouble breathing. I had gone in to check on her just a few minutes before; although she was not feeling well, she reached out and touched my hand as I examined her. Five minutes later, the code bell alarmed. She lay limp in bed, lifeless. Her face was covered in blood, which we knew came from her lungs.

My colleague and I placed a breathing tube and the nursing team performed CPR and administered all of the proper medications. The tube was in the right place, the medications were getting in, everything was happening right on time--but she remained lifeless.

Her oxygen saturation was too low for her to resuscitate, so we put her on a heart-lung bypass machine. Although we were able to get her onto the machine, and her heart was revived, we learned once again the lesson that ICU clinicians hate: The brain is the most sensitive organ to low oxygen delivery. It had all been taken away from her in the 20 minutes her brain had been deprived of oxygen. She died three days later.”

After this tragic event, Dr. Kheir began investigating the idea of injectable oxygen while he was still a fellow. “I knew that this was a big problem that nobody had an answer for," says Dr. Kheir. "Why couldn’t we just make a form of oxygen that we could inject into an intravenous line? I found that there was a whole field of research focusing on gas-filled microbubbles that people used for ultrasound contrast agents and for targeted therapy. Maybe we could alter that technology to be able to safely inject oxygen gas.”

In the early days, he and colleagues at Columbia University tested various microbubble preparations with their own blood, drawing blue, deoxygenated blood from their veins and adding the microbubble preparation – which quickly turned the blood red again.

The microparticles, consisting of oxygen gas encased in a single layer of lipids (fatty molecules) and suspended in liquid, mix well with blood and appear safe when tested in animals.

“The microparticle solutions are portable and can buy paramedics, emergency clinicians and ICU clinicians time in critical situations, before a breathing tube or mechanical ventilation can be started, “says Kheir.

“This is a short-term oxygen substitute – a way to safely inject oxygen gas for a few minutes in patients with obstructed airways,” he says. “We could potentially put several syringes of this on every code cart in the hospital to help stabilize patients who are having difficulty breathing.”

Recently reported in Science Translational Medicine, the microbubble solution was injected intravenously into rabbits with low blood oxygen levels, which caused the restoration of blood oxygen saturation within seconds to near-normal levels. When the trachea was completely blocked – a more dangerous “real world” scenario -- the microparticles kept the animals alive and reduced the incidence of cardiac arrest and organ injury.

Since these first studies and with funding for Boston Children’s Technology Development Fund, Dr. Kheir and colleagues have tweaked the concentrations and size of the microparticles to optimize their effectiveness. They are also continuing to refine their manufacturing technique.

Dr. Kheir has continued his passionate work on this technology with the hopes of bring the technology to save his patient's lives. “We have many obstacles to overcome to bring this idea to a patient’s bedside,” says Dr. Kheir. Boston Children’s Hospital is seeking industry partners to advance the IV oxygen delivery technology into clinical use.

[Editor's Note: For more information or to learn about partnership opportunities related to this technology, please contact Boston Children's Technology and Innovation Development Office or phone (617) 919-3019.]

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