Oral rehydration therapy

A person with cholera drinking oral rehydration solution (ORS)

ORT may lower the mortality rate of diarrhea by as much as 93%.[2] Case studies in four developing countries also have demonstrated an association between increased use of ORS and reduction in mortality.[11] ORT using the original ORS formula has no effect on the duration of the diarrheic episode or the volume of fluid loss,[12] although reduced osmolarity solutions have been shown to reduce stool volume.[13]

The degree of dehydration should be assessed before initiating ORT. ORT is suitable for people who are not dehydrated and those who show signs and symptoms of mild to moderate dehydration. People who have severe dehydration should seek professional medical help immediately and receive intravenous rehydration as soon as possible to rapidly replenish fluid volume in the body.[14]

UNICEF-WHO Oral Rehydration Salt (ORS) packet

In 2003, WHO and UNICEF recommended that the osmolarity of oral rehydration solution be reduced from 311 to 245 mOsm/L.[26][27] These guidelines were also updated in 2006. This recommendation was based on multiple clinical trials showing that the reduced osmolarity solution reduces stool volume in children with diarrhea by about twenty-five percent and the need for IV therapy by about thirty percent when compared to standard oral rehydration solution. The incidence of vomiting is also reduced. The reduced osmolarity oral rehydration solution has lower concentrations of glucose and sodium chloride than the original solution, but the concentrations of potassium and citrate are unchanged.[28][13][29][30]

The reduced osmolarity solution has been criticized by some for not providing enough sodium for adults with cholera.[31] Clinical trials have, however, shown reduced osmolarity solution to be effective for adults and children with cholera.[30] They seem to be safe but some caution is warranted according to the Cochrane review.[30]

As part of oral rehydration therapy, the 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.[35]

After severe dehydration is corrected and appetite returns, feeding the person speeds the recovery of normal intestinal function, minimizes weight loss and supports continued growth in children. Small frequent meals are best tolerated (offering the child food every three to four hours). Mothers should continue to breastfeed.[22][11][36] A child with watery diarrhea typically regains their 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, the WHO recommends giving the child an extra meal each day for two weeks, and longer if the child is malnourished.[22]

Dehydration may be overestimated in wasted children and underestimated in edematous children.[37] Care of these children must also include careful management of their malnutrition and treatment of other infections. Useful signs of dehydration include an 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 moderate 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.[22]

The original ORS (90 mmol sodium/L) and the current standard reduced-osmolarity ORS (75 mmol sodium/L) both contain too much sodium and too little potassium for severely malnourished children with dehydration due to diarrhea. ReSoMal (Rehydration Solution for Malnutrition) is recommended for such children. It contains less sodium (45 mmol/L) and more potassium (40 mmol/L) than reduced osmolarity ORS.[38] It can be obtained in packets produced by UNICEF or other manufacturers.

An exception is if the severely malnourished child also has severe diarrhea (in which case ReSoMal may not provide enough sodium), in which case standard reduced-osmolarity ORS (75 mmol sodium/L) is recommended.[22] Malnourished children should be rehydrated slowly. The WHO recommends 10 milliliters of ReSoMal per kilogram body weight for each of the first two hours (for example, a 9-kilogram child should be given 90 mL of ReSoMal 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 lethargic. If the child drinks poorly, a nasogastric tube should be used. The IV route should 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.[22]

Feeding should usually resume within 2–3 hours after starting rehydration and should continue every 2–3 hours, day and night. For an initial cereal diet before a child regains his or her full appetite, the 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. Give 130 mL per kilogram of body weight during per 24 hours. A child who cannot or will not eat this minimum amount should be given the diet by nasogastric tube divided into six equal 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, the child should be eating 200 mL per kilogram of body weight per 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. Children who are breastfed should continue breastfeeding.[22]

The 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.[22]

If cholera is suspected give an antibiotic to which V. cholerae are susceptible. This reduces the volume loss due to diarrhea by 50% and shortens the duration of diarrhea to about 48 hours.[39]

In the early 1980s, "oral rehydration therapy" referred only to the preparation 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".[34]

Crane and his sketch of the sodium-glucose symporter

Refugee camp near Goma

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 changes in blood composition and loss of water and salt in the stool of people with cholera and prescribed intravenous fluid therapy (IV fluids), first administered by Latta. The prescribing of hypertonic IV therapy by Rogers 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.[43]

In 1953, Indian physician Hemendra Nath Chatterjee published his results in The Lancet of treating people with mild cholera with ORT.[44] He gave the solution orally and rectally along with Coleus extract, antihistimines and antiemetics without controls. The formulation of the fluid replacement solution was 4 g of sodium chloride, 25 g of glucose and 1000 mL of water.[44][45] He did not publish any balance data and his exclusion of patients with severe dehydration did not lead to any confirmatory study; his report remained anecdotal.

Robert Allan 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, and he used to try to stop the diarrhea rather than to rehydrate patients.

In the early 1960s, biochemist Robert K. Crane described the sodium-glucose co-transport mechanism and its role in intestinal glucose absorption.[46] 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.[47][48] In 1968, David R. Nalin and Richard A. Cash, assisted by Rafiqul Islam and Majid Molla, 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.[49][46]

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, 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.[43][45] 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 ORT and began a global program for its dissemination.

In the 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.[50][51][52] 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 sugar and a three-finger pinch of salt. Later on, the approach was broadcast over television and radio and a market for oral rehydration salts packets developed. Three decades later, national surveys have found that almost 90% of children with severe diarrhea in Bangladesh are given oral rehydration fluids at home or in a health facility.[53] ORT is known in Bangladesh as Orosaline or Orsaline.

From 2006 to 2011, UNICEF estimated that worldwide about a third of children under 5 who had diarrhea received an oral rehydration solution, with estimates ranging from 30% to 41% depending on the region.[54][55]

ORT is one of the principal elements of the UNICEF "GOBI FFF" program (growth monitoring; ORT; breast feeding; immunization; female education; family spacing and food supplementation). The program aims to increase child survival in developing nations through proven low-cost interventions.[56]

People had fled from civil war in Mozambique to southern Malawi. In November 1990, cholera broke out in a refugee camp in southern Malawi where approximately 74,000 persons were temporarily living. David Swerdlow of the U.S.'s CDC Epidemic Intelligence Service (EIS) wrote about the situation. He recommended setting up a tent just for children who would be assisted by some of the best nurses. He recommended against over-reliance on IV tubes, which often were left attached to persons for a week or more and which could lead to infections and septic shock. And he noticed that sick persons were not drinking enough rehydration solution. He assigned so-called "ORS officers" whose job was to encourage persons to drink more solution.[57]

It was a minor mystery how persons were getting sick since deep-bore wells provided clean water and refugees were encouraged to wash their hands. It was then discovered that the only place for persons to wash hands were in the same buckets in which water was transported and stored. Swerdlow wrote in his report, "Use of narrow mouthed water containers would probably decrease the likelihood of contamination."[57]