The Platonic cliché says that necessity is the mother of invention, but in the case of Japanese scientist Takanori Takebe, it is more correct to speak of paternity.
Sick with a lung infection, his father needed to be intubated and, given the serious risks that mechanical ventilation can cause to the lungs, the son appealed to the unusual: what if mammals, like some fish, could breathe through the rectum?
“Fortunately, he survived, but when I saw it was just luck, I started thinking urgently about alternative forms of breathing,” he told leaf the gastroenterologist, who is a professor at Cincinnati Children’s Hospital Medical Center (USA) and at Tokyo Medical and Dental University, a Japanese institution protagonist in this research.
Used in patients with respiratory failure, such as those with severe Covid conditions, or those undergoing major procedures, mechanical ventilation is an invasive procedure that can generate numerous complications.
The most common are pneumonia and pulmonary trauma, but cardiac and circulatory complications can also occur, according to Marcelo Alcântara Holanda, pulmonologist of the Intensive Care Committee of the Brazilian Society of Pulmonology and Phthisiology and one of the creators of Elmo, an assisted breathing helmet used with success in Covid-19 patients in Ceará.
It was at this moment of anguish that Takebe’s curiosity entered the picture. The researcher recalled that aquatic animals, such as the American catfish and the sea spider, are endowed with intestinal breathing mechanisms to survive under hypoxia, a condition of lack of oxygen.
The scientist then joined a large team to find out if the mechanism could also work in mammals. The experiments carried out with rats, mice and pigs consisted of depriving the animals of oxygen and testing different forms of insertion through the anus.
In the first experiment, gaseous oxygen was used, which achieves the best results if combined with scraping the rectal mucus, but the alternative was abandoned: the practice can be harmful to the digestive system.
When intact, the intestinal mucosa acts as a barrier, preventing the passage of certain substances and also microorganisms, explain proctologist brothers Bruno and Marcelo Giusti Werneck Cortes, respectively president and marketing director of Sociedade Mineira de Coloproctologia.
In other words, intentionally injuring the intestinal mucosa is not a risk-free procedure, since it loses its protective function against the passage of potentially harmful agents, such as bacteria and viruses, into the bloodstream and the entire organism.
In the second test, scientists on Takebe’s team used oxygenated PFC (perfluorocarbon), an oxygen-rich aqueous solution known to be versatile and compatible with the human body. Inserted rectally, the liquid facilitated the exchange of gases with the surface of the intestine.
In the control group, which did not have any type of intervention, none of the animals survived for more than 11 minutes. In the group that received gaseous oxygen and had the mucus scraped, the survival rate was 75%, and the animals withstood an average of 50 minutes in extreme oxygen deprivation.
Animals that received the aqueous PFC solution had similar results and, in both cases, there were no side effects—but the authors point out that possible long-term impacts have not been studied.
Gas exchange in the intestine is only possible because the mammalian rectum has a complex vascular network connected to the systemic circulation. This is nothing new: there are medications that are commonly administered via the rectum and are known for their quick action.
They can be used for local action or in cases where the oral route is contraindicated, such as when the patient has irritation in the upper digestive system or is unable to swallow, for example.
The absorption of drugs through the rectum can be very fast, depending on the formulation used, and it is an important way of applying drugs in emergency situations, such as seizures in children, say proctologists Marcelo and Bruno Giusti.
Even so, it is important to know that the oxygenation technique is far from being applied in human treatments. Research needs to go through other stages, and clinical incorporation can take up to a decade.
There is currently no ongoing research to study enteral ventilation in humans. Takebe hopes it will be possible to start one in 2022 through the startup he founded, EVA Therapeutics Inc (EVA is the acronym for enteral ventilation via the anus).
“It is the first time that the subject is studied, but it is interesting to note that 400 years ago a slightly similar method, although not the same, was used in traditional medicinal practices”, says the scientist.
He refers to a traditional North American Indian practice, the tobacco smoke enema. The method consisted of blowing tobacco smoke into the anus of sick people through a long tube. Initially, smoke was applied for revival and warming, especially for drowning victims.
With the colonization of North America, the Europeans imported the technique and started to use it for the most varied demands. There are reports of uses of tobacco smoke enema for simple purposes, such as headaches and colds, even hernias, typhoid and cholera.
The practice, however, fell out of favor in the 17th century, when British physician Benjamin Brodie demonstrated the toxicity of nicotine.
Scientists who continue studies of enteral ventilation will have many questions to answer and limitations to work around. It will be necessary to discover, for example, how to reconcile the use of the rectum for breathing with the physiological needs of the digestive system, such as evacuation itself.
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