Flushing trillions of tiny oxygen bubbles through the rectum increases blood oxygen in pigs and could be an alternative to ventilation for people with damaged lungs
15 December 2021
The injection of trillions of tiny oxygen bubbles into the rectum has been shown to raise blood oxygen levels and lower carbon dioxide levels in pigs whose lungs were damaged by smoke. The researchers are now seeking the go-ahead to do safety tests of the procedure in healthy volunteers.
The approach could help people, whatever the cause of their low blood oxygen. For instance, people with covid-19 often come into hospitals with very low oxygen levels, says Robert Scribner at Respirogen, a Colorado-based company set up to commercialise the approach.
“This could be a good bridging therapy to raise the oxygen saturation in those patients,” he says, and it might mean they don’t need to be put on a ventilator, which can have many harmful side effects.
While the pig tests lasted only a few hours, the treatment should work over longer periods, says team member Keely Buesing at the University of Nebraska Medical Center.
“There’s no reason why you couldn’t just cycle these oxygen microbubbles in and out of the body,” she says. “With the colonic delivery method, it could in theory be a long-term sustaining therapy for severely injured patients, we just haven’t tested it out to those time points.”
The key to the approach is that the oxygen is enclosed in micrometre-sized bubbles of fat, says team member Mark Borden at the University of Colorado, Boulder, who originally developed these microbubbles in the 1990s to improve ultrasound scans. Compared with pure oxygen gas, the tiny bubbles enormously increase the surface area and allow much more oxygen to diffuse through the colon into the bloodstream, he says.
For the pig tests, 12 pigs weighing between 40 and 50 kilograms were exposed to smoke. After two days, their blood oxygen saturation had dropped to 66 per cent on average. Colonic infusion of microbubbles in six pigs raised this to 81 per cent after 150 minutes. In the animals that weren’t treated, oxygen saturation fell to 53 per cent. The pigs were kept sedated throughout the procedure.
In addition, blood carbon dioxide levels fell in the treated pigs as it diffused into the microbubbles, while it kept rising in the animals that weren’t treated. This is important because high carbon dioxide has many adverse effects including impairing thinking, says Buesing.
“Your mental status declines to a point where you can no longer protect your airway,” she says.
Takanori Takebe at the Tokyo Medical and Dental University carried out a similar study in pigs earlier this year, but using a fluid called perfluorocarbon that can hold high levels of oxygen. He says the advantage of using oxygen microbubbles instead is that it should be easier to get regulatory approval than with perfluorocarbon, but that further studies will be needed to confirm how effective it is.
Takebe is continuing to develop the perfluorocarbon approach. His group has set up a company called EVA Therapeutics, which is planning to do a human trial in 2022.
The Respirogen team thinks oxygen microbubbles will prove to be more effective than perfluorocarbon. Perfluorocarbon – made famous by its portrayal as a breathing liquid in the film The Abyss – can hold a lot of oxygen, Borden says, but it doesn’t release it all, and might not remove carbon dioxide.
Reference: bioRxiv, DOI: 10.1101/2021.12.08.466665
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