Oral rehydration therapy

Oral rehydration therapy (ORT) involves giving water with modest amounts of sugar and salt, with the aim of preventing or remedying dehydration. A key element of ORT is that water is still absorbed from the gastrointestinal tract into the body, even with loss of fluid through diarrhea or vomiting. The World Health Organization (WHO) recommends starting oral rehydration as soon as possible after an episode of diarrhea begins; and recommends starting with available home liquids and fluids including (but not limited to): salted rice water, unsalted rice water, salted vegetable broth, unsalted vegetable broth, weak unsweetened tea, salted yoghurt drink, unsalted yoghurt drink, green coconut water, unsweetened fresh fruit juice, as well as plain water. WHO states, “Other fluids should be recommended that are frequently given to children in the area, that mothers consider acceptable for children with diarrhea, and that mothers would be likely to give in increased amounts when advised to do so.” In responding to diarrhea, WHO recommends giving children under two years of age a quarter- to half-cup of fluid following each loose bowel movement, and older children more, and in general giving the person as much fluid as he or she wishes to drink.

In the case of vomiting, WHO recommends a pause of 5–10 minutes and then restarting the fluid more slowly. Vomiting often occurs during the first hour or two of rehydration, but this rarely prevents successful rehydration since most of the fluid is absorbed. After this time vomiting usually stops.

ORT adjunctive treatments include the administration of zinc supplements for two weeks, teaching family members the warning signs of moderate to severe dehydration, and the encouragement of the patient with diarrhea to continue to eat if at least some appetite is still present as this helps to speed recovery of normal intestinal function. Often, frequent smaller meals are tolerated better. Most children with watery diarrhea regain their appetite soon after dehydration is remedied, whereas children with bloody diarrhea often eat poorly until their illness resolves.

Health organisations offer a number of differing recipes for making ORT at home using plain clean water as its basis. Some publications recommend one teaspoon of salt and six teaspoons sugar added to one litre of water, although others recommend only half a teaspoon of salt and six teaspoons of sugar added to one litre of water. Rehydration Project states, " Making the mixture a little too diluted (with more than 1 litre of clean water) is not harmful." Commercial preparations are also available as either pre-prepared fluids or packets of oral rehydration salts (ORS) ready for mixing with water.

ORT can be given by parents or other family members in a home setting. ORT can also be given by aid workers or health care workers in refugee camps, health clinic or hospital settings.

A child with both dehydration and malnutrition should be rehydrated relatively slowly in order to avoid flooding the circulation and overloading the heart. Specifically, WHO recommends giving such a child 10 milliliters of oral rehydration solution per kilogram of body weight for the first hour (for example, a 9-kilogram child should be given 90 milliliters of solution the first hour). This rate of hydration should be continued for another hour and then more slowly based on the child's thirst and ongoing stool losses, keeping in mind that a severely dehydrated child may be lethargic. Increasing edema is a sign of over-hydration. If a child drinks poorly, a nasogastric tube can be used. An IV should only be used by a medical professional and again relatively slowly. In cases of severe malnutrition, the usual signs of infection, such as fever, are often absent. In particular, a malnourished child who has signs suggesting severe dehydration but without a history of watery diarrhea should be treated for septic shock. WHO recommends that all severely malnourished children admitted to a hospital should receive broad spectrum antibiotics. Feeding should usually resume within two to three hours of starting rehydration and should continue every two to three hours, and mothers should remain with their children if at all possible.

Since its introduction and development for widespread use in the latter part of the 20th century, oral rehydration therapy has decreased human deaths from dehydration in vomiting and diarrheal illnesses, especially in cholera epidemics occurring in children. It represents a major advance in global public health.

Effectiveness
Prior to the introduction of ORT, death from diarrhea was the leading cause of infant mortality in developing nations. Between 1980 and 2006, the introduction of ORT is estimated to have decreased the number of deaths, worldwide, from 5 to 3 million per year. However, in 2008, diarrhea remained the second most common cause of death in children under five years (17 percent), (after pneumonia (19 percent)). Moreover, by the same year, the use of ORT in children under five had declined.

Physiological basis
Fluid from the body enters the intestinal lumen during digestion. This fluid is isosmotic with the blood because it contains a high concentration of sodium (approx. 142 mEq/L). A healthy individual secretes 20–30 grams of sodium per day into the intestinal lumen. Nearly all of this is reabsorbed so that sodium levels in the body remain constant. In a diarrheal illness, sodium-rich intestinal secretions are lost before they can be reabsorbed. This can lead to a life-threatening hyponatraemia within hours. This is the motivation for sodium and water replenishment in ORT.

Sodium absorption from the intestine occurs in two stages. The first is via intestinal epithelial cells. Sodium passes into these cells by co-transport via the SGLT1 protein. From the intestinal epithelia cells, sodium is pumped by active transport via the sodium potassium pump through the basolateral membrane into the extracellular space. The sodium–potassium ATPase pump at the basolateral membrane of the cell moves three sodium ions into the extracellular space, whilst pulling into the cell two potassium ions. This creates a "downhill" sodium gradient within the cell. SGLT proteins use energy from this downhill sodium gradient to transport glucose across the apical membrane of the cell against the glucose gradient. The co-transporters are examples of secondary active transport. The GLUT uniporters then transport glucose across the basolateral membrane. Both SGLT1 and SGLT2 are known as symporters, since both sodium and glucose are transported in the same direction across the membrane.

The co-transport of glucose into epithelial cells via the SGLT1 protein requires sodium. Two sodium ions and one molecule of glucose (as galactose) are transported together across the cell membrane via the SGLT1 protein. Without sodium, intestinal glucose is not absorbed. This is why oral rehydration salts (ORS) include both sodium and glucose. For each cycle of the transport, hundreds of water molecules move into the epithelial cell, slowly rehydrating the patient.

Low-osmolarity oral rehydration salts
WHO and UNICEF jointly maintain official guidelines for the manufacture of oral rehydration salts (ORS). In 2003, clinical trials and comparisons with rice water led to a reduction in the recommended osmolarity of ORS. The guidelines were also updated in 2006. The reduced osmolarity ORS has a total osmolarity of 245 mmol/L. It decreases vomiting; decreases stool volume by about twenty-five percent; and the need for IV therapy by about thirty percent. When the recommended osmolarity of ORS was reduced from 311 mmol/L to 245 mmol/L, the concentration of glucose and sodium chloride were reduced, while that of potassium and citrate remained the same.

Basic ORT solutions
A basic oral rehydration therapy solution is composed of salt, sugar, and water in solution, made using a standard ratio For example,
 * 30 ml sugar : 2.5 ml salt : 1 liter water
 * 6 tsp. sugar : 0.5 tsp. 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 manufactured, reduced osmolarity ORS packets. These guidelines are used by commercial manufacturers of ORS packets and were last updated in 2006. The reduced osmolarity ORS has a total osmolarity of 245 mmol/L.

The WHO and UNICEF guidelines suggest home-made ORT should begin at the first sign of diarrhea in order to prevent dehydration. Recommendations for home-made ORT fluid recipes vary. However, there are some consistent principles.

The molar ratio of sugar to salt should be 1:1 and the solution should not be hyperosmolar. The Mayo clinic suggests half a teaspoon of salt, six level teaspoons of sugar and 1 L water. The British Columbia health service suggests sugar free fruit juice mixed with water in a ratio of 1:4.

Babies are given ORT fluid from a dropper or a syringe. Infants under two are given a teaspoon of ORT fluid every one to two minutes. Older children and adults take sips from a cup. If the patient vomits, the carer waits a short time then persists with the ORT.

Ideally, water for mixing with ORS is boiled or treated with chlorine. However, ORS is not withheld on the basis of potentially unsafe water. Rehydration takes precedence.

Zinc
As part of oral rehydration therapy, WHO recommends supplemental zinc (10 to 20 mg daily) for ten to fourteen days, to reduce the severity and duration of the illness and make recurrent illness in the following two to three months less likely. Preparations are available as a zinc sulfate solution for adults, a modified solution for children and in tablet form.

Feeding
Continuing to feed the patient, when some appetite is present, speeds the recovery of normal intestinal function, as well as supporting continued nutrition, growth and weight gain in children. Small frequent meals are best tolerated (offering the child food every three to four hours). Mothers should continue to breastfeed. A child with watery diarrhea typically regains his or her appetite as soon as dehydration is corrected, whereas a child with bloody diarrhea often eats poorly until the illness resolves. Such children should be encouraged to resume normal feeding as soon as possible. Once diarrhea is corrected, WHO recommends giving the child one more meal a day for two weeks, and longer if the child is malnourished.

Children with malnutrition
Dehydration may be overestimated in wasted children and underestimated in edematous children. Care of these children must also include careful management of their malnutrition and treatment of other infections. Useful signs of dehydration remain eagerness to drink, lethargy, cool and moist extremities, weak or absent radial pulse (wrist), and reduced or absent urine flow. In children with severe malnutrition it is often impossible to reliably distinguish between some dehydration and severe dehydration. A severely malnourished child who has signs of severe dehydration but who does not have a history of watery diarrhea should be treated for septic shock.

Since the previous ORS (90 mmol sodium/L) and the current standard reduced-osmolarity ORS (75 mmol sodium/L) both have too much sodium and too little potassium for the typical severely malnourished child, the Bangladesh Institute of Public Health Nutrition recommends Rehydration Solution for Malnutrition (ReSoMal). An exception is if the severely malnourished child also has severe diarrhea (in which case ReSoMal may not provide enough sodium), then standard reduced-osmolarity ORS (75 mmol sodium/L) is recommended.

The Bangladesh Institute of Public Health Nutrition further recommends that the IV route not be used for rehydration except in cases of shock and then only with care, infusing slowly to avoid flooding the circulation and overloading the heart. In addition, with severe acute malnutrition, the usual signs of infection, such as fever, are often absent, and infections are often hidden, and it's therefore recommended that all severely malnourished children be treated with broad-spectrum antibiotics on admission.

The World Health Organization's THE TREATMENT OF DIARRHOEA: A manual for physicians and other senior health workers also recommends rehydrating malnourished children slowly. Specifically, WHO recommends 10 milliliters of ORS per kilogram body weight for each of the first two hours (for example, a 9-kilogram child should be given 90 ml of ORS over the course of the first hour, and another 90 ml for the second hour) and then continuing at this same rate or slower based on the child's thirst and ongoing stool losses, keeping in mind that a severely dehydrated child may be lethagic. If the child drinks poorly, a nasogastric tube should be used. IV infusion should only be used for the treatment of shock and then slowly to avoid over-hydration and heart failure. Increasing edema is a sign of over-hydration.

WHO also states that standard reduced-osmolarity ORS (75 mmol sodium/L) contains too much sodium and too little potassium. And therefore, WHO recommends modifying the solution by adding one packet to two liters of water, adding 45 ml of potassium chloride solution from a stock solution containing 100g KCl/liter, and adding 50 grams of sucrose to the two liters. This will result in a solution with less sodium, more potassium, and more sugar, each of which is appropriate for severely malnourished children with diarrhea. This is best mixed by a medical professional in a clinic setting. If this is not available, refer to the previous recommendations about starting promptly with available home remedies such as salted rice water, unsalted rice water, salted vegetable broth, unsalted vegetable broth, weak unsweetened tea, plain water, etc.

Feeding should usually resume within 2-3 hours of starting rehydration, and food should be given every 2-3 hours, day and night. Mothers should remain with their children if at all possible. WHO recommends continuing breastfeeding and perhaps even re-lactating if circumstances realistically allow. As an example of an initial cereal diet before a child regains his or her full appetite, WHO recommends combining 25 grams skimmed milk powder, 20 grams vegetable oil, 60 grams sugar, and 60 grams rice powder or other cereal into 1,000 milliliters water and boiling gently for five minutes. A child should be feed 130 ml per kilogram of body weight during one day (for example, a 9-kilogram child should be given 1,170 ml of this initial food over the course of a day). A child who cannot or will not eat this minimum amount should be given the diet by nasogastric tube divided into six feedings. Later on, the child should be given cereal made with a greater amount of skimmed milk product and vegetable oil and slightly less sugar. As appetite fully returns, a child will be eating 200 ml per kilogram of body weight during a day (a 9-kilogram child should be given 1,800 ml of this modified cereal over the course of a day). Zinc, potassium, vitamin A, and other vitamins and minerals should be added to both recommended cereal products, or to the oral rehydration solution itself. Some mothers exclusively breastfeed for the first six months of an infant's life, and this has health advantages. WHO states, "In general, foods suitable for a child with diarrhoea are the same as those required by healthy children."

WHO recommends that all severely malnourished children admitted to hospital should receive broad spectrum antibiotics (for example, gentamicin and ampicillin). In addition, hospitalized children should be checked daily for other specific infections.

Definition
In the early 1980s, the term oral rehydration therapy referred only to the solution prescribed by the World Health Organization (WHO) and UNICEF. In 1988, the definition changed to encompass recommended home-made solutions, because the official preparation was not always readily available. The definition was again amended in 1988 to include continued feeding as an appropriate associated therapy. In 1991, the definition became, "an increase in administered hydrational fluids" and in 1993, "an increase in administered fluids and continued feeding".

Development
Over 2,500 years ago, the Indian physician Sushruta described the treatment of acute diarrhea with rice water,coconut water, and carrot soup.

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 cholera patients and prescribed intravenous fluid therapy (IV fluids). The prescribing ofhypertonic 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 1957, Hemendra Nath Chatterjee, a physician of India, published his results of treating patients with cholera with ORT. However, he had not performed a controlled trial. Robert A. Phillips attempted to create an effective ORT solution based on his discovery that, in the presence of glucose, sodium and chloride become absorbable during diarrhea in patients with cholera. Phillips did not succeed due to inadequate methodology.

In the early 1960s, Robert K. Crane, a biochemist, discovered the sodium-glucose co-transport mechanism and its role in intestinal glucose absorption. This strengthened belief in the concept that the intestinal mucosa is not disrupted in cholera and led to understanding of the physiological basis of the effectiveness of ORT. In 1960, David R. Nalin found that in adults, ORT given in volumes equal to that of the diarrhea, reduces the need for IV fluid therapy by eighty percent.

In 1971, the Bengali people fought for independence from Pakistan. The fighting displaced many people and an epidemic of cholera ensued. When IV fluid ran out in the refugee camps, Dilip Mahalanabis, a physician, instructed his staff to distribute oral rehydration salts (ORS) to family members and carers. Over 3,000 patients with cholera received ORT in this way. The mortality rate was 3.6 percent with ORT and 30 percent with IV fluid therapy.

As an example of the implementation of ORT, in 1980 the Bangladeshi nonprofit BRAC essentially developed a door-to-door and person-to-person sales force to teach ORT. A task force of fourteen women, one cook, and one male supervisor traveled from village to village, figuring the supervisor would protect them from others, and the women’s numbers would protect them from the supervisor. After visiting with women in the village, each evening they got together and talked about what worked and what didn’t. They hit upon the method of encouraging the women in the village to themselves go through the steps of making oral rehydration fluid. And they used available household equipment, starting with a “half a seer” (half a quart) of water and adding a fistful of sugar and a three-finger pinch of salt. Later on, these changes were sustained with television and radio and the development of a market for oral rehydration salt packets. Three decades later, national surveys have found that almost 90% of children with severe diarrhea in Bangladesh are given oral rehydration fluid.

From 2006 to 2011, UNICEF estimated that worldwide about a third of children under 5 who had diarrhea received oral rehydration solution, with estimates ranging from 30% to 41% depending on the region of the world.

ORT is one of the principle elements of the UNICEF "GOBI FFF" program (growth monitoring; ORT; breast feeding; immunisation; female education; family spacing and food supplementation). The program aims to increase child survival in developing nations through low-cost interventions.

Awards

 * Centre for Health and Population Research, Dhaka, Bangladesh, 2001 Gates award for global health.
 * Norbert Hirschhorn, Dilip Mahalanabis, David Nalin, and Nathaniel F. Pierce, 2002 inaugural Pollin Prize for Pediatric Research.
 * Richard A. Cash (Harvard School of Public Health), David Nalin (Albany Medical College), Dilip Mahalanabis (public health) and Stanley G. Schultz (medicine), 2006 Prince Mahidol Award.

Controversy and ongoing investigations
The ORS formulation has been criticised for not providing enough sodium for adults with cholera.

In Rwanda, a charity supplied the sports drink, Gatorade, which is not indicated in ORT in children and was accused of making them worse.

The president of AmeriCares, the said charity, responded,
 * "We stand by our decision to ship Gatorade to Rwandan refugees. In the absence of potable water, Gatorade, with its electrolytes and water, saved countless lives in a true triage situation."