Systemically injected oxygen within rapidly dissolving microbubbles improves the outcomes of severe hypoxaemia in swine
Acute respiratory failure can cause profound hypoxaemia that leads to organ injury or death within minutes. When conventional interventions are ineffective, the intravenous administration of oxygen can rescue patients from severe hypoxaemia, but at the risk of microvascular obstruction and of toxicity of the carrier material. Here we describe polymeric microbubbles as carriers of high volumes of oxygen (350-500 ml of oxygen per litre of foam) that are stable in storage yet quickly dissolve following intravenous injection, reverting to their soluble and excretable molecular constituents. In swine with profound hypoxaemia owing to acute and temporary (12 min) upper-airway obstruction, the microbubble-mediated delivery of oxygen led to: the maintenance of critical oxygenation, lowered burdens of cardiac arrest, improved survival, and substantially improved neurologic and kidney function in surviving animals. Our findings underscore the importance of maintaining a critical threshold of oxygenation and the promise of injectable oxygen as a viable therapy in acute and temporary hypoxaemic crises.
Authors
- David M. Harrild (ORCID: https://orcid.org/0009-0002-0670-5215)
- Brian D. Polizzotti (ORCID: https://orcid.org/0000-0002-0871-1064)
- Alan B. Packard (ORCID: https://orcid.org/0000-0003-0906-1021)
- Jay Hartford
- Edward Yang (ORCID: https://orcid.org/0000-0002-9912-4163)
- Kristen Sack
- Alexis R. Cole (ORCID: https://orcid.org/0000-0003-3317-793X)
- John N. Kheir (ORCID: https://orcid.org/0000-0001-6080-8739)
- Hart G.W. Lidov (ORCID: https://orcid.org/0000-0002-1839-7603)
- Simon Keith Warfield (ORCID: https://orcid.org/0000-0002-7659-3880)
- Julia García Mancebo
- Yifeng Peng (ORCID: https://orcid.org/0000-0002-1273-8171)
- Francesca Sperotto (ORCID: https://orcid.org/0000-0001-7109-0582)
- Arthur Nedder
- Saffron Dominguez
- Michelle Balcarcel‐Monzon
- Tien Nguyen (ORCID: https://orcid.org/0000-0003-0872-0881)
- Jason L.J. Dearling (ORCID: https://orcid.org/0000-0002-8117-3098)
- Allen D. Everett
- Elizabeth Chartier
Institutions
- Boston Children's Hospital (US)
- Harvard University (US)
- Johns Hopkins University (US)
- Boston Children's Museum (US)
Publication Details
- Journal
- Nature Biomedical Engineering
- Published
- 2024-10-17
- DOI
- https://doi.org/10.1038/s41551-024-01266-8
- Citations
- 3
- Primary Topic
- Cardiac Arrest and Resuscitation
- Type
- article
- Field-Weighted Citation Impact
- 2.07
Funders
- National Science Foundation
- U.S. Department of Defense
- National Institutes of Health
- National Heart, Lung, and Blood Institute