Oral rehydration therapy
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Oral rehydration therapy (ORT) is a medical treatment consisting of liquid solutions delivered orally which are designed to counteract dehydration. Also known as Oral Rehydration Solution (ORS) or Oral Rehydration Salts (ORS), ORT is often used in conjunction with, or as a replacement for, IV Fluid treatments.
ORT solutions vary in composition, but usually contain a mixture of glucose, sodium, potassium, and citrate. In some cases, ORT solutions using products available in the home, such as salted rice water, yogurt drinks, or vegetable or chicken soups, may be used.
Numerous case studies, including those conducted by the WHO, have shown that ORT dramatically reduces the number of deaths experienced during and after epidemics of cholera. The ease of administering ORT, which can be given by non-medical personnel, has resulted in ORT being heralded as one of the most significant public health advances in the 20th century.
Prescriptions from the ancient Indian physician Sushruta date back over 2500 years with treatment of acute diarrhea with rice water, coconut juice, and carrot soup. However, this knowledge did not carry over to the Western world, as dehydration was found to be the major cause of death secondary to 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 cholera patients and prescribed intravenous fluid therapy (IV) to compensate. The results were remarkable, as patients who were on the brink of death from dehydration recovered. The mortality rate of cholera dropped from 70 percent to 40 percent with the use of hypertonic IV solutions. IV fluid replacement became entrenched as the standard of care for moderate/severe dehydration for over a hundred years. ORT replaced it with the support of several independent key advocates that ultimately convinced the medical community of the efficacy of ORT.
In the late 1950s, ORT was prescribed by Dr. Hemendra Nath Chatterjee in India for patients diagnosed with cholera. Although his findings predate physiological studies, his results failed to gain credibility and recognition because they did not provide scientific controls and detailed analysis. Credit for discovery that in the presence of glucose, sodium and chloride became absorbable during diarrhea (in cholera patients) is typically ascribed to Dr. Robert A. Phillips. However, early attempts to translate this observation into an effective oral rehydration solution failed, due to incorrect solution formula and inadequate methodology.
In the early 1960s, biochemist Robert K. Crane discovered the sodium-glucose cotransport as the mechanism for intestinal glucose absorption. Around the same time, others showed that the intestinal mucosa was not disrupted in cholera, as previously thought. These findings were confirmed in human experiments, where it was first shown that a glucose-saline oral therapy solution administered in quantities matching measured diarrhea volumes was effective in significantly decreasing the necessity for IV fluids by 80 percent. These results helped establish the physiological basis for the use of ORT in clinical medicine.
The events surrounding the Bangladesh Liberation War in 1971 convinced the world of the effectiveness of ORT. As medical teams ran out of intravenous fluids to treat the spreading cholera epidemic, Dr. Dilip Mahalanabis instructed his staff to distribute oral rehydration salts (ORS) to the 350,000 people in refugee camps. Over 3,000 patients with cholera were treated, and the death rate was only 3.6 percent, compared with the typical 30 percent seen in intravenous fluid therapy. The fact that ORT was delivered primarily by family members instead of trained staff across such a large population in an emergency fashion was demonstrative proof of the utility of ORT against cholera.
Between 1980 and 2006, ORT decreased the number of deaths that occurred worldwide from 5 million a year to 3 million a year. Death from diarrhea was the leading cause of infant mortality in the developing world until ORT was introduced. It is now the second leading cause of mortality for children under five, accounting for 17 percent of all deaths, second only to pneumonia, at 19 percent. Its remarkable success has led to naming the discovery of its underlying physiological basis as "potentially the most important medical advance [of the 20th] century." ORT is part of UNICEF's GOBI program, a low cost program to increase child survival in developing countries, including growth monitoring, ORT, breastfeeding, and immunization. Despite the success and effectiveness of ORT, its uptake has recently slowed and even reversed in some developing countries. This raises concerns for increased mortality from diarrhea and highlights the need for effective community-level behavioral change and global funding and policy.
The individuals and organizations involved in the development of ORT have been recognized widely. The 2001 Gates Award for Global Health was awarded to the Centre for Health and Population Research, located in Dhaka, Bangladesh, for its role in the development of ORT. In 2002, the first Pollin Prize for Pediatric Research was awarded to Dr. Norbert Hirschhorn, Dr. Dilip Mahalanabis, Dr. David Nalin, and Dr. Nathaniel F. Pierce for their contributions in the discovery and implementation of ORT. For promoting the use of ORT, the 2006 Prince Mahidol Award was awarded to Dr. Richard A. Cash of Harvard School of Public Health, Dr. David Nalin of Albany Medical College, and Dr. Dilip Mahalanabis in the field of public health; and to Dr. Stanley G Schultz in the field of medicine.
The World Health Organizations states that some home products can be used to treat and prevent dehydration. This includes salted rice water, salted yogurt drink, and salted vegetable or chicken soup. A home-made solution of one litre of plain water with 3 grams table salt (one half level teaspoonful) and 18 grams common sugar (three tablespoons) can also be made. And a medium amount of salt can also be added to water in which cereal has been cooked, unsalted soup, green coconut water, unsweetened weak tea, and unsweetened fruit juice. The homemade solution should have the "taste of tears." If available, supplemental zinc and potassium can be added to or given with the homemade solution.
ORT is available anywhere that adequate nutrition is available. ORS, on the other hand, is typically packaged in pre-measured sachets that are ready to be mixed in with water (generally 1L). These are available via commercial manufacturers or supplied by local/regional governments or relief agencies such as UNICEF. In 1996, UNICEF distributed 500 million sachets of ORS to over 60 developing nations. Commercial suppliers produce a variety of formulations, and there is no restriction as to what formulation can be marketed as ORS. As such, some vendors include extra sugar or other flavoring to make the product more palatable, popular examples in the US being the various flavors and formulations of Drip Drop ORS,Frutolyte and Pedialyte.
Scheduled to start in October 2011,[dated info] there is a pilot program in Zambia that will test to what extent piggybacking ORS and zinc on Coca-Cola's distribution channels could improve access to these medicines, particularly in rural areas. The project, called Colalife uses the empty spaces in crated bottles of Coke to supply wedge-shaped packets of medicine that contain oral rehydration salts.
The definition of ORT has changed over time, broadening in scope and encompassing a definition of a specific therapy appropriate for rehydration. Initially, in the early 1980s, ORT was defined only as the solution prescribed by the WHO/UNICEF. It was later changed in 1988 to encompass recommended home fluids, because the official preparation was not always readily available. It was amended once again in 1988 to include continued feeding as appropriate management. In 1991, the definition was changed to define ORT as any increase in administered hydrational fluids. The final change came in 1993, and is the definition used today, which states that ORT is an increase in administered fluids and continued feeding.
WHO/UNICEF definition of ORS 
|sodium chloride (NaCl)||2.6||45|
|glucose, anhydrous (C6H12O6)||13.5||75|
|potassium chloride (KCl)||1.5||20|
|trisodium citrate, dihydrate
Basic solution 
- 30 ml sugar: 2.5 ml salt : 1 liter water
- 2 tbl. sugar : 0.5 tsp. salt : 1 quart water
The WHO and UNICEF jointly maintain the official guidelines for the contents of reduced osmolarity ORS packets. These guidelines are used by manufacturers of commercial ORS packets that are available for purchase and were last updated in 2006. The reduced osmolarity ORS has a total osmolarity of 245 mmol/L.
Switch to reduced osmolarity ORS 
In 2003, WHO/UNICEF changed the ORS formula to a reduced osmolarity version from what it had been recommending for over two decades prior. This change was in response to numerous studies that showed that the standard ORS formula was ineffective in reducing diarrheal stool output compared to other solutions, including rice water. Additionally, further studies showed that a reduced osmolarity solution not only decreased stool output, but also resulted in less vomiting and fewer unscheduled intravenous therapy cases. Although UNICEF certifies reduced osmolarity ORS for all forms of dehydration, at least one study cautions that for high stool output cholera-based diarrhea, reduced osmolarity ORS may not sufficiently replenish electrolyte levels, leading to hyponatremia. Though the actual consequence of this appeared negligible, further study was recommended.
The change reduced the osmolarity of the ORS from 311 mmol/L to 245 mmol/L. The ingredients reduced in concentration were glucose and sodium chloride. Potassium and citrate concentrations remained the same. The benefits of the reduced osmolarity ORS are reducing stool volume by about 25 percent, reducing vomiting by nearly 30 percent, and reducing the need for unscheduled intravenous therapy by 33 percent.
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Current WHO/UNICEF guidelines, recommend that ORT should begin at home with "home fluids" or a home-prepared "sugar and salt" solution at the first sign of diarrhea to prevent dehydration. The fluids given must contain both sugar and salt in the proper amounts. Liquids without salt can lead to low body salt (hyponatremia) because the diarrheal stool contains salt that must be replenished. Additionally, sugar must also be present in the administered fluid because salt absorption is coupled with sugar in the intestine via the SGLT1 transporter. Feeding should be continued at all times. After initial fluid volume has been restored, the regimen should be switched to official preparations of oral rehydration salts (ORS) at the appropriate dosing times to maintain adequate hydration and proper electrolyte balance.
Other appropriate treatments include official ORSs, salted rice water, salted yogurt-based drinks, and vegetable or chicken soup with salt. Clean water should always be used when preparing a solution. Drinks with diuretic properties (due to high sugar content and/or caffeine) should be avoided. Drinks with a high concentration (osmolarity) of sugar can worsen diarrhea as they draw water out of the body and into the intestine because of their hypertonicity.
Food and supplements 
An adult or child with diarrhea should continue to eat, and infants should continue to breast-feed. In a 2005 publication for doctors regarding the treatment of diarrhea, the World Health Organization states: "When food is given, sufficient nutrients are usually absorbed to support continued growth and weight gain. Continued feeding also speeds the recovery of normal intestinal function, including the ability to digest and absorb various nutrients. In contrast, children whose food is restricted or diluted lose weight, have diarrhea of longer duration, and recover intestinal function more slowly."
Zinc supplementation is recommended for the management of diarrheal disease in addition to ORS, particularly for pediatric patients. For children under five, zinc supplementation significantly reduces the severity and duration of diarrhea and is strongly recommended as a supplement with ORS for dehydrated children. Preparations are available as a zinc sulfate solution for adults, a modified solution for children, and also a tablet form for children.
Treatment when malnourished 
Dehydration may be overestimated in a marasmic/wasted child and underestimated in a kwashiorkor/edematous child. The diagnosis is based instead on whether the person has been having diarrhea. Rehydration Solution for Malnutrition (ReSoMal) contains less salt and more sugar and potassium than regular ORS. In addition, the World Health Organization recommends that all malnourished individuals with diarrhea be treated with a course of broad-spectrum antibiotics. Supplemental zinc is still recommended, and a dehydrated person should still continue to be given food.
Physiological basis 
Fluid from the body is normally pumped into the intestinal lumen during digestion. This fluid is typically isosmotic with blood because it contains a high concentration of sodium (approx. 142 mEq/L). A healthy individual will secrete 20-30 grams of sodium per day via intestinal secretions. Nearly all of this is reabsorbed by the intestine, helping to maintain constant sodium levels in the body (homeostasis).
Because there is so much sodium secreted by the intestine, without intervention, heavy continuous diarrhea can become a potentially life-threatening condition within hours. This is because liquid secreted into the intestinal lumen during diarrhea passes through the gut so quickly that little sodium is reabsorbed, leading to dangerously low sodium levels in the body (severe hyponatremia). This is the motivation for sodium and water replenishment via ORT.
Sodium absorption via the intestine occurs in two stages. The first is at the outermost cells (intestinal epithelial cells) at the surface of the intestinal lumen. Sodium passes into these outermost cells by co-transport via the SGLT1 protein. From there, sodium is pumped out of the cells (basal side) and into the extracellular space by active transport via the sodium potassium pump.
The co-transport of sodium into the epithelial cells via the SGLT1 protein requires glucose or galactose. Two sodium ions and one molecule of glucose/galactose are transported together across the cell membrane through the SGLT1 protein. Without glucose or galactose present, intestinal sodium will not be absorbed. This is the reason glucose is included in ORSs. For each cycle of the transport, hundreds of water molecules move into the epithelial cell, slowly rehydrating the affected individual.
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