Each of us will probably experience diarrhea, However, the progress of medicine has made us no longer have the fear of dying from diarrhea. However, only a few decades ago, the death caused by diarrhea was still a very serious health threat in developing countries. The opportunity to reverse this situation came from the emergence of an unusually simple treatment method-oral rehydration (ORS).
However, behind this seemingly simple treatment plan, there are many unknown twists and turns. The beginning of this story begins with a group of young researchers who devoted themselves to finding effective treatments for cholera-like diarrhea more than 50 years ago.
Cholera is an acute diarrhoeal disease caused by Vibrio cholerae, Due to the massive loss of body fluids and electrolytes, Can rapidly cause circulatory failure, Serious cases can kill people within hours. Since modern times, There have been several cholera pandemics in human history, Each epidemic resulted in a large number of deaths, In the summer of 1932, there was a cholera epidemic in China. A total of 95,000 cholera cases were recorded nationwide, killing 31,000 people. The case fatality rate in Peiping was even more appalling as high as 80%. This was simply a merciless killing of human beings by nature. In the face of natural disasters, human beings always do a little what with self-righteousness, but many practices may be worse than inaction.
In 1972 Norman Howard-Jones described the methods for early people to treat cholera as follows: Throughout the history of disease treatment before the 20th century, There is nothing more absurd than the treatment of cholera. It was basically a kind of well-intentioned killing.] The regions most affected by cholera for the longest time are the Ganges Delta region in India and Bangladesh. Most of the cholera pandemics in human history spread from here, and the research on cholera also began here. In 1962, when the seventh world pandemic of cholera broke out, a group of young American scholars came to the Ganges Delta and were determined to snipe at the killing.
As early as 1950, Swedish doctor Per Selander advocated carrot soup to treat diarrhea. Isn’t this some kind of oral [rehydration]? But at that time Selander had not been able to elucidate the mechanism by which oral rehydration was effective against diarrhea. At that time, the academic circles did not recognize the idea that oral rehydration could treat diarrhea at all, Because the idea at that time was that the gastrointestinal tract of children with diarrhea could not absorb liquid, Therefore, it is necessary to fast in the treatment process to give the gastrointestinal tract a chance to rest and recover. In addition to fasting, the treatment measures at that time also included comprehensive measures such as intravenous infusion and blood transfusion … After such ordeals, children with diarrhea often need to be hospitalized for 2 weeks.
In those days, the mortality rate of diarrhoea patients was still relatively high, which should be related to the poor nutritional status caused by this crude treatment method and fasting. Generally speaking, doctors at that time still lacked understanding of the pathophysiology of diarrhoea patients and the transportation routes of water and electrolytes in the human body.
In the 1940s, Danel Darrow of Yale University conducted pioneering research on electrolytes in the human body. And has caused repercussions in the scientific community, Based on these studies, Darrow began to suggest correcting dehydration by supplementing liquids such as glucose, potassium and sodium chloride. In 1949, he wrote in an article: [Effective fluid infusion therapy for diarrhea and dehydration patients should be based on an accurate understanding of the composition of human body fluids and their pathological changes], he proposed that potassium, lactic acid and glucose oral liquid can help patients recover lost water and electrolyte, thus avoiding [long-term parenteral therapy].
Darrow’s intravenous infusion combined with oral liquid treatment resulted in a mortality rate of less than 5% for infants with moderate to severe dehydration. After 18 years, Based on Darrow’s theory and practice, the improved and standardized oral electrolyte and glucose solution became the widely known oral rehydration therapy. More importantly, Darrow laid a foundation for future medical research, that is, in the clinical research stage, it is not appropriate to blindly decide which treatment method is the most effective.
Before Darrow, There are also doctors who have tried oral rehydration for diarrhea patients based on experience. Sometimes salt is added to the water, sometimes sodium bicarbonate, sugar or lactic acid are added, but the ratio is not accurate, and the therapeutic effect can be imagined. For example, the concentration of salt and sugar in the liquid ingested by some people is relatively large, and its osmotic pressure is greater than that of human body fluid, which will inevitably lead to further aggravation of the degree of dehydration and will not achieve the effect of fluid replacement.
Darrow’s research did not directly lead to the emergence of modern oral rehydration therapy. It is related to one of his misconceptions, because he does not think that oral rehydration therapy can be used as a good remedy for dehydration alone, but is only a transitional measure between intravenous infusion and diet restoration, that is to say, he did not intend to develop a simple, practical and suitable oral therapy for promotion.
In 1953, physiologists R. B. Fisher and D. S. Parsons of Oxford University discovered the mechanism of glucose transport in the small intestinal wall of rats. This is a key component in clarifying the mechanism of rehydration therapy. Unfortunately, As pure physiologists, their research did not involve fluid infusion and human tests. However, they deepened Darrow’s research and inspired other researchers to extensively study the electrolyte transport mechanism in intestinal canal. Since the absorption mechanism of glucose is so mysterious, is electrolyte absorption special? Following in their footsteps, physiologists Riklis and Quastel published important conclusions on sugar absorption in 1958. Glucose absorption depends on the existence of sodium ion channels. They also began to explore the optimal concentration conducive to glucose, water and sodium absorption. Finally Schultz, Curran and Zalusky established the coupling mechanism of glucose-sodium ion absorption.
However, when Darrow initially added glucose to the oral fluid taken by the patient, However, the existence of glucose-sodium ion absorption coupling mechanism is not recognized, His original intention was to increase the absorbable energy substances for patients, but in fact the glucose component in modern oral rehydration salts is mainly to promote the absorption of liquid, not to provide calories. A scholar who opposes blind methods to solve clinical problems has gone in the right direction this time.
Like many basic medical studies, Schultz et al’s research results were not quickly applied to the treatment of diarrhea, But scientists firmly believe that, With the thorough understanding of the mechanism of body fluid environment in basic medicine, It is bound to have great application value in diagnosis and treatment of related fields. At this time, The seventh world pandemic of cholera broke out, and several U.S. Research teams went to Egypt, India, Bangladesh and the Philippines to conduct research. It was these people who found a sharp weapon to end cholera killings and had a profound impact on the treatment of diarrhea.
Dr. Robert A. Phillps’ research on cholera began in 1947, This time, He sent the Naval Medical Research Institute formerly based in Taiwan to Manila, Philippines. At the St. Lhasa Hospital, The improved intravenous infusion therapy summarized by Phillps for many years was used to treat cholera. The mortality rate can be as low as 3.4% (at the same time, the mortality rate is as high as 30% ~ 40% in villages that do not have the conditions to receive such treatment). In further research, Phillps observed that when oral electrolyte liquid is given to patients, if glucose is added, sodium absorption will be greatly promoted, which surprises Phillps. Isn’t this the fact discovered by scientists such as Schultz and Curran in the laboratory?
According to researchers familiar with Phillps and his work, He was trying to find a way to reduce sodium but keep the solution isotonic. He chose glucose only to maintain the molar concentration of the liquid, His exploration was carried out independently. Further research confirmed that Oral therapy is feasible for cholera patients. Today, scholars studying oral rehydration therapy still admire Phillps’ findings. This independent discovery greatly strengthens the value of the coupling mechanism of glucose-sodium ion transport and absorption discovered in previous animal experiments, And overturned the traditional idea that diarrhoea patients need hunger therapy. A few years later, scholars have been able to use oral therapy alone to treat cholera patients. Oral therapy is still effective even for patients with serious illness. Some doctors have successfully reduced the rate of intravenous infusion by 80%.
In April 1968, An article published in the Lancet said: [By taking oral fluids containing glucose and electrolytes, the intravenous infusion rate of adult cholera patients can be reduced by three quarters.] So far, the efficacy of oral rehydration therapy has been proved, and subsequently it has been proved that this therapy can also be applied to dehydration caused by non-cholera-like diarrhea, as well as to children.
But ironically, This great research, mainly led by American scholars, matured outside the United States. In the 1970s, When these scholars want to popularize this achievement in the United States, However, it was unexpectedly met with cold reception. Because many American doctors think that oral rehydration, such a simple therapy, cannot have such excellent curative effect. They think that this therapy is only suitable for those backward developing countries. The United States is a developed industrialized country. Oh, we have intravenous infusion! The United States, which has dominated many advances in the medical field, There was also a history of blind superstition of infusion. Since entering the era of evidence-based medicine, There is stronger evidence that, In most cases (intravenous infusion is of course the first choice for severe cases of shock due to dehydration), for the treatment of diarrhea, oral rehydration therapy has no significant difference in the therapeutic effect of shortening the course of disease compared with intravenous infusion therapy. Moreover, oral rehydration therapy can also reduce the occurrence of adverse reactions and reduce hospitalization time.
In February 1994, The United Nations Children’s Fund and the International Centre for the Study of Diarrhoeal Diseases organized meetings, Politicians and international health advocates gathered in Dhaka, Bangladesh. To commemorate the 20th anniversary of oral rehydration therapy, a life-saving technique that saves countless lives, He also called on the medical profession to pay more attention to this simple life-saving technique. Oral rehydration therapy can be effectively applied in the world’s most backward regions and can save the lives of millions of children every year. As of this year, this therapy is the 40th year of its birth, and more than tens of millions of people have died because of this therapy.
Author: Li Morning
This article is authorized by the author to be published by Clove Garden.