Injected Microbubbles Offer Safe Way to Deliver Emergency Oxygen

For years, researchers and clinicians have been searching for an effective way to quickly deliver oxygen to patients in situations where traditional oxygenation methods are inadequate or difficult, particularly during cardiac or respiratory arrest. In some cases, severe hypoxemia caused by airway obstruction or lung disease makes conventional techniques to increase oxygen levels, such as the insertion of a breathing tube, ineffective. This can lead to cardiac arrest, which may result in severe organ damage. Studies have shown that low oxygen levels trigger up to 40% of in-hospital cardiac arrests. Now, 15 years of research have led to the successful development of a safe and effective method of oxygen delivery using injectable oxygen carried into the bloodstream by a rapidly dissolving gas microbubble.

While it may seem counterintuitive that a small injection of oxygen could make a difference in a system that circulates around 200 milliliters of oxygen per minute in adults, researchers at Boston Children’s Hospital (Boston, MA, USA) have long believed that if oxygen was delivered via an injectable gas carrier at the right time and location, it could have a meaningful effect. They just needed time to prove their hypothesis. Initially, the team experimented with lipid-coated microbubbles, but these bubbles would clump together in the bloodstream, posing a serious risk of lethal embolism unless injected at a highly controlled rate. This failure led them to realize that the bubbles needed to be designed to prevent such coalescence. A second attempt involved hollow-core polymeric microparticles, but these failed to deliver a meaningful amount of oxygen into circulation. The researchers then returned to the drawing board for a third attempt.

Image: Big syringe, little bubbles: John Kheir, MD, holds the microbubbles that aim to provide emergency oxygen (Photo courtesy of Michael Goderre/Boston Children’s Hospital)

Their latest design incorporates the best elements from previous approaches. The new oxygen carrier is a microbubble engineered with a solid polymer shell that, upon being triggered by blood pH, dissolves into tiny soluble molecules that can then be safely excreted by the body. This structure ensures the drug remains stable in storage and can be injected in critical situations like cardiac arrest. In pre-clinical testing, these specially designed pH-sensitive microbubbles delivered the required amounts of oxygen and significantly improved survival rates by preventing catastrophic organ damage. Their research is the first to demonstrate that a gas carrier for oxygen can be safely and rapidly delivered in large doses to animals. The key to their success is ensuring the microbubble dissolves quickly to avoid blood-flow obstruction. This breakthrough opens the door for future clinical trials, and the team is excited about the potential impact of their innovation.

“This opens a door to potentially creating a controlled and predictable way of providing necessary oxygen during hypoxemia, cardiac arrest, and other shock states,” said Boston Children’s cardiologist John Kheir, MD. “It’s exciting. It’s not just a potential solution for this medical issue. It’s a platform technology. There are a lot of other gases we can put in and there are a lot of other medical situations suitable for a focused amount of gas delivery. The possibilities of what we can do with a drug like this are numerous.”

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Boston Children’s Hospital