By Dr Muhammad Azrul Zabidi
The urgent need for reliable alternatives to traditional blood transfusions has driven global scientific innovation for decades. While scientists worldwide race to develop universal oxygen carriers, a recent, highly unconventional discovery, the possibility of human respiration through the rectum, or “butt breathing” has captured medical attention, suggesting a revolutionary new paradigm for emergency respiratory support.
The unconventional enteral ventilation via anus (EVA)
The PFC technology developed for artificial blood is now central to one of the most surprising recent discoveries: enteral ventilation via anus (EVA), popularly referred to as ‘butt breathing’ or ‘bottom breathing’.
Inspired by aquatic organisms like loaches, which use their posterior intestines as an accessory organ for air breathing when oxygen levels are low, researchers explored whether this capability could be adapted for mammals.
The mammalian rectum is highly vascularised, featuring a relatively thin mucosal layer around the anal canal and abundant vascular drainage through hemorrhoidal plexuses connected to both the portal and systemic circulation. This anatomical feature makes the distal gut a potential site for efficient gas exchange.
Researchers, including Dr. Takanori Takebe, developed two main EVA methods: delivering pure oxygen gas (g-EVA) or oxygenated liquid (l-EVA) via the rectum. The liquid form, liquid-EVA, utilizes oxygen-loaded perfluorocarbon (PFC) or perfluorodecalin (PFD), a compound historically used safely in clinics for liquid ventilation through the airway. PFD is crucial because it has a remarkable capacity to adsorb both oxygen (O2) and carbon dioxide (CO2).
In pre-clinical trials using mice and pigs with severe respiratory failure, l-EVA proved highly tolerable and effective. In pigs, for instance, repeated doses of O2-loaded PFD increased blood oxygen saturation (SpO2) by 15% and arterial oxygen pressure (PaO2) by 13 mm Hg. These results demonstrated that liquid-EVA successfully oxygenated the systemic circulation and alleviated respiratory failure symptoms.
Crucially, safety features assessed in rats and pigs showed no obvious short-term side effects, with Perfluorocarbon levels in the blood remaining below the limit of quantification.
Following these animal successes, researchers have conducted safety tests in healthy human volunteers in Japan, administering non-oxygenated PFD liquid via enema. While some patients receiving high doses experienced mild discomfort or bloating, most tolerated the procedure well. This successful safety test sets the stage for future clinical trials using the oxygen-loaded liquid to determine if it can reliably deliver oxygen to the human bloodstream.
Hope for respiratory emergencies
Following successful animal models, researchers in Japan recently tested the safety of administering non-oxygenated PFD liquid via enema in 27 healthy human volunteers. While high doses caused mild discomfort or bloating in some subjects, most tolerated the procedure well. Encouragingly, high doses led to a slight increase in oxygen levels, suggesting that oxygen absorption is feasible in humans.
The development of EVA is not meant to replace normal lung function, but rather to serve as an adjunctive support for patients facing critical respiratory distress. This includes patients suffering from severe conditions like pneumonia or Acute Respiratory Distress Syndrome (ARDS), particularly those affected by events like the SARS-CoV-2 pandemic, which severely strained the supply of conventional ventilators and artificial lungs (ECMO).
Physicians envision EVA being used in emergency situations, such as during hospital transfers, or as a short-term intervention to stabilize patients when placing them on life support, potentially mitigating dangerously low oxygen levels.
While some experts remain sceptical, arguing that the lungs are inherently superior for gas exchange, the possibility of using this “second route” for oxygen delivery offers hope in scenarios where conventional options are unavailable or inadequate.
This research, which earned an Ignoble (Ig) Nobel Prize for science that “makes you laugh, then think,” demonstrates that highly unconventional medical ideas, fuelled by advancements in materials like PFCs, can open revolutionary new avenues for saving lives.
Dr Muhammad Azrul Zabidi is a Senior Lecturer at the Advanced Medical and Dental Institute, Universiti Sains Malaysia
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