page_title: Oral rehydration therapy
section_title: Development
hierarchical_section_title: Oral rehydration therapy / History / Development
caption_attribution_description: English: This picture is of Dr Robert K. Crane and his sketch on a piece of napkin for coupled cotransport that he proposed at the international meetings in Prague in 1960. The sketch shows brush-border membrane supposedly of the intestinal epithelium showing the digestive surface and the diffusion barrier. During digestion the dietary glucose liberated from sucrose at the digestive surface is transported across the plasma membrane by a sodium-glucose carrier complex. Glucose transport is driven by the inward Na+ gradient maintained by the Na+ pump. Strophanthidin inhibits the Na+ pump causing the Na+ gradient to dissipate and remove the driving force for uphill glucose transport. Phlorizin inhibits cotransport. The model remains valid to this day, apart from some minor details such as the site of phlorizin inhibition (extracellular) and the location of the Na+/K+ pump.
context_page_description: Oral rehydration therapy is a type of fluid replacement used to prevent and treat dehydration, especially that due to diarrhea. It involves drinking water with modest amounts of sugar and salts, specifically sodium and potassium. Oral rehydration therapy can also be given by a nasogastric tube. Therapy should routinely include the use of zinc supplements. Use of oral rehydration therapy has been estimated to decrease the risk of death from diarrhea by up to 93%.
  Side effects may include vomiting, high blood sodium, or high blood potassium. If vomiting occurs, it is recommended that use be paused for 10 minutes and then gradually restarted. The recommended formulation includes sodium chloride, sodium citrate, potassium chloride, and glucose. Glucose may be replaced by sucrose and sodium citrate may be replaced by sodium bicarbonate, if not available. It works as glucose increases the uptake of sodium and thus water by the intestines. A number of other formulations are also available including versions that can be made at home. However, the use of homemade solutions has not been well studied.
context_section_description: Until 1960, ORT was not known in the West. Dehydration was a major cause of death during the 1829 cholera pandemic in Russia and Western Europe. In 1831, William Brooke O'Shaughnessy noted the loss of water and salt in the stool of people with cholera and prescribed intravenous fluid therapy (IV fluids). The prescribing of hypertonic IV therapy decreased the mortality rate of cholera from 70 to 40 percent. In the West, IV therapy became the "gold standard" for the treatment of moderate and severe dehydration.
  In 1953 Indian physician Hemendra Nath Chatterjee published his results in The Lancet of treating people with cholera with ORT. He was the first to formulate and demonstrate the effectiveness of ORS for diarrhea. The formulation of the fluid replacement solution  was 4 g of sodium chloride, 25 g of glucose and 1000 ml of water.
  Robert A. Phillips attempted to create an effective ORT solution based on his discovery that, in the presence of glucose, sodium and chloride could be absorbed in patients with cholera. However, Phillips' efforts failed because the solution he used was excessively hypertonic.
  In the early 1960s, biochemist Robert K. Crane described the sodium-glucose co-transport mechanism and its role in intestinal glucose absorption. This, combined with evidence that the intestinal mucosa appears undamaged in cholera, suggested that intestinal absorption of glucose and sodium might continue during the illness. This supported the notion that oral rehydration might be possible even during severe diarrhea due to cholera. In 1967–1968, Norbert Hirschhorn and Nathaniel F. Pierce, working in Dhaka, Bangladesh and Calcutta, India, respectively, showed that people with severe cholera can absorb glucose, salt and water and that this can occur in sufficient amounts to maintain hydration. In 1968, David R. Nalin and Richard A. Cash reported that in adults with cholera, given an oral glucose-electrolyte solution in volumes equal to that of the diarrhea losses, reduced the need for IV fluid therapy by eighty percent.
  Rafiqul Islam (c. 1936 – 5 March 2018) was a Bangladeshi physician and medical scientist. He is known for the discovery of food saline (Orosaline) for the treatment of diarrhea. In 1971, fighting during the Bangladesh Liberation War displaced millions and an epidemic of cholera ensued among the refugees. When IV fluid ran out in the refugee camps, Rafiqul Islam and Dilip Mahalanabis, a physician working with the Johns Hopkins International Center for Medical Research and Training in Calcutta, instructed to prepare and distribute an oral rehydration solution prepared from individual ingredients to family members and caregivers. Over 3,000 people with cholera received ORT in this way. The mortality rate was 3.6 percent among those given ORT compared with 30 percent in those given IV fluid therapy. It was also known as "Dhaka Saline". After the independence of Bangladesh, a wide circulation campaign was conducted on the use of saline in the treatment of diarrhea.  In the year 1980, the World Health Organization recognized Orosaline.
  In the early 1970s, Norbert Hirschhorn used oral rehydration therapy on the White River Apache Indian Reservation with a grant from the National Institute of Allergy and Infectious Diseases. He made the important observation that children would voluntarily drink as much of the solution as needed to restore hydration, and that rehydration and early re-feeding would protect their nutrition. This led to increased use of ORT for children with diarrhea, especially in developing countries.
  In 1980 the Bangladeshi nonprofit BRAC created a door-to-door and person-to-person sales force to teach ORT for use by mothers at home. A task force of fourteen women, one cook and one male supervisor traveled from village to village. After visiting with women in several villages, they hit upon the idea of encouraging the women in the village to make their own oral rehydration fluid. They used available household equipment, starting with a "half a seer" (half a quart) of water and adding a fistful of s
caption: Crane and his sketch of the sodium-glucose symporter
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