Oral rehydration therapy

From Wikipedia, the free encyclopedia
Jump to: navigation, search
Oral rehydration therapy
Cholera rehydration nurses.jpg
A person with cholera drinking oral rehydration solution (ORS)
MeSH D005440
eMedicine 906999-treatment

Oral rehydration therapy (ORT) is a fluid replacement strategy used to prevent or treat dehydration. Dehydration is most commonly caused by diarrhea. It involves drinking water with modest amounts of sugar and salt added, while continuing to eat. Routine therapy also includes supplemental zinc. Caretakers are taught the signs of dehydration and/or worsening dehydration. The World Health Organization and UNICEF specify indications, preparations and procedures for ORT.[1]

Vomiting seldom prevents successful management of dehydration since much of the fluid is still absorbed. If the person vomits, the World Health Organization (WHO) recommends taking a pause of five to ten minutes and then restarting the solution more slowly. For example, a child under two can be given a teaspoonful of fluid every two to three minutes. Older people can take frequent sips from a cup.[1]

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 diarrheal illnesses, especially in cholera epidemics and in children. It represents a major advance in global public health. It is on WHO's List of Essential Medicines, a list of the most important medication needed in a basic health system.[2]

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 infant deaths, worldwide, from 5 to 3 million per year.[3][4] However, in 2008, diarrhea still remained the second most common cause of death in children under five years (17 percent), (after pneumonia (19 percent)).[5] Moreover, by the same year, the use of ORT in children under five had declined.[6]

In situations where an oral rehydration solution (ORS) is not available, homemade solutions are sometimes used.[7] However, there is currently insufficient evidence to recommend usage of these homemade solutions.[8]

Medical uses[edit]

ORT is less invasive than the other strategies for fluid replacement, specifically intravenous (IV) fluid replacement. Mild to moderate dehydration in children seen in an emergency department is best treated with ORT. Persons taking ORT should eat within 6 hours and return to their full diet within 24–48 hours.[9]

Oral rehydration therapy may also be used as a treatment for the symptoms of dehydration and rehydration in burns in resource-limited settings.[10]


ORT may lower the mortality rate of diarrhea by as much as 93%.[8] Case studies in 4 developing countries also demonstrated an association between increased use of ORT and reduction in mortality.[11]

Treatment algorithm[edit]

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.[12]


ORT should be discontinued and fluids replaced intravenously when vomiting is protracted despite proper administration of ORS, signs of dehydration worsen despite giving ORT, the person is unable to drink due to a decreased level of consciousness, or there is evidence of intestinal blockage or ileus. ORT might also be contraindicated in people who are in hemodynamic shock due to impaired airway protective reflexes.[13] Short-term vomiting is not a contraindication to receiving oral rehydration therapy. In persons who are vomiting, drinking oral rehydration solution at a slow and continuous pace will help the vomiting to resolve.[9]


Examples of commercially available oral rehydration salts. On the left from Nepal. On the right from Peru.

WHO and UNICEF jointly have developed official guidelines for the manufacture of ORS and describe acceptable alternative preparations, depending on material availability. Commercial preparations are available as either pre-prepared fluids or packets of oral rehydration salts (ORS) ready for mixing with water.[14][15]

The formula for ORS originally recommended by WHO and UNICEF in 1975 was 3.5 grams (0.12 oz) salt (NaCl), 2.9 grams (0.10 oz) trisodium citrate dihydrate (C
), 1.5 grams (0.053 oz) potassium chloride (KCl), 20 grams (0.71 oz) anhydrous glucose (C
) per litre of fluid.[16] This provides 90 mEq sodium, 80 mEq chloride, and 20 mEq potassium per litre of fluid as well as a total osmolarity of 311 mOsm/l.[17]

A basic oral rehydration therapy solution can also be prepared when packets of oral rehydration salts are not available. It can be made using 6 level teaspoons of sugar and 0.5 teaspoon of salt in 1 litre of water.[18][19] The molar ratio of sugar to salt should be 1:1 and the solution should not be hyperosmolar.[20] The Rehydration Project states, "Making the mixture a little diluted (with more than 1 litre of clean water) is not harmful."[21]

The optimal fluid for preparing ORS solution is clean water. However, if this is not available the usually available water should be used. ORS should not be withheld simply because the available water is potentially unsafe. Rehydration takes precedence.[1]

When ORS packets and suitable teaspoons for measuring sugar and salt are not available, WHO has recommended that home made gruels, soups, etc. may be considered to help maintain hydration.[22] A Lancet review in 2013 emphasized the need for more research on appropriate home made fluids to prevent dehydration.[23]

Reduced-osmolarity oral rehydration salts[edit]

Pakistani children hold low-osmolarity oral rehydration packets and other drugs to treat diarrhea.

In 2003, WHO and Unicef recommended that the osmolarity of ORS be reduced from 311 to 245 mOsm/l .[24] 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 ORS. The incidence of vomiting is also reduced. The reduced osmolarity ORS has lower concentrations of glucose and sodium chloride than the original ORS, but the concentrations of potassium and citrate are unchanged.[25][26][27][28][29][30]

The reduced osmolarity ORS has been criticized by some for not providing enough sodium for adults with cholera.[31] Clinical trials have, however, shown reduced osmolarity ORS to be both safe and effective for adults and children with cholera.[29][30]


ORT is based on evidence that water continues to be absorbed from the gastrointestinal tract even while fluid is lost through diarrhea or vomiting.

WHO/UNICEF guidelines suggest ORT should begin at the first sign of diarrhea in order to prevent dehydration.[32][33] Babies may be given ORS with a dropper or a syringe. Infants under two may be given a teaspoon of ORS fluid every one to two minutes. Older children and adults should take frequent sips from a cup. WHO recommends giving children under two a quarter- to a half-cup of fluid following each loose bowel movement and older children a half- to a full cup. If the person vomits, the carer should wait 5–10 minutes and then resume giving ORS.[1](Section 4.2) ORS may be given by aid workers or health care workers in refugee camps, health clinics and hospital settings.[34] Mothers should remain with their children and be taught how to give ORS. This will help to prepare them to give ORT at home in the future. Breastfeeding should be continued throughout ORT.[1]

Associated therapies[edit]


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.[35]


Feeding the person after severe dehydration is corrected and appetite returns 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.[1][36][37] 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 an extra meal each day for two weeks, and longer if the child is malnourished.[1]

Children with malnutrition[edit]

Dehydration may be overestimated in wasted children and underestimated in edematous children.[38] Care of these children must also include careful management of their malnutrition and treatment of other infections. Useful signs of dehydration include 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.[1]

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.

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.[1] Malnourished children should be rehydrated slowly. 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 lethagic. 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. [1]

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, 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 breast fed should continue breastfeeding.[1]


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.[1]

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]

Physiological basis[edit]

Intestinal epithelium (H&E stain)

Fluid from the body enters the intestinal lumen during digestion. This fluid is isosmotic with the blood and contains a high about 142 mEq/L of sodium. A healthy individual secretes 2000–3000 milligrams 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 life-threatening hypovolemia within hours when fluid loss is severe. The objective of therapy is the replenishment of sodium and water losses by ORT or intravenous infusion.[40]

Sodium absorption occurs in two stages. The first is via intestinal epithelial cells (enterocytes). Sodium passes into these cells by co-transport with glucose, via the SGLT1 protein. From the intestinal epithelial cells, sodium is pumped by active transport via the sodium-potassium pump through the basolateral cell membrane into the extracellular space.[41][42]

The sodium–potassium ATPase pump at the basolateral cell membrane moves three sodium ions into the extracellular space, while 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 (or galactose) are transported together across the cell membrane via the SGLT1 protein. Without glucose, intestinal sodium is not absorbed. This is why oral rehydration salts include both sodium and glucose. For each cycle of the transport, hundreds of water molecules move into the epithelial cell to maintain osmotic equilibrium. The resultant absorption of sodium and water can achieve rehydration even while diarrhea continues.[40]



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]


Dr. Crane and his sketch of the sodium-glucose symporter
Refugee camp.

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.[43]

In 1957 Indian physician Hemendra Nath Chatterjee published his results of treating people with cholera with ORT.[44] 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 could be avsorbed in patients with cholera. However, Phillips efforts failed because the solution he used was excessively hypertonic.[45]

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 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]

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 his staff 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]

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.[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]

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; immunisation; female education; family spacing and food supplementation). The program aims to increase child survival in developing nations through proven low-cost interventions.[56]




  1. ^ a b c d e f g h i j k l "The treatment of diarrhea, a manual for physicians and other senior health workers." World Health Organization, 2005.
  2. ^ "WHO Model List of EssentialMedicines" (PDF). World Health Organization. October 2013. Retrieved 22 April 2014. 
  3. ^ Gerline, A. (8 October 2006). "A simple solution". Time. 
  4. ^ "Water with sugar and salt". Lancet 312 (8084): 300–1. August 1978. doi:10.1016/S0140-6736(78)91698-7. 
  5. ^ The state of the world's children: child survival (PDF). UNICEF. December 2007. p. 8. ISBN 978-92-806-4191-2. 
  6. ^ Ram PK, Choi M, Blum LS, Wamae AW, Mintz ED, Bartlett AV (March 2008). "Declines in case management of diarrhoea among children less than five years old". Bull. World Health Organ. 86 (3): E–F. doi:10.2471/BLT.07.041384. PMC 2647400. PMID 18368194. 
  7. ^ Martínez-Salgado, H; Calva-Mercado, JJ; Mota-Hernández, F; Posadas-Tello, L; Bross-Soriano, D (Aug 1991). "[Efficacy of a rice-based beverage for the management of dehydration caused by acute diarrhea in children].". Boletin medico del Hospital Infantil de Mexico 48 (8): 544–53. PMID 1953974. 
  8. ^ a b Munos, MK; Walker, CL; Black, RE (April 2010). "The effect of oral rehydration solution and recommended home fluids on diarrhoea mortality.". International Journal of Epidemiology. 39 Suppl 1: i75–87. doi:10.1093/ije/dyq025. PMID 20348131. 
  9. ^ a b Nutrition Committee, Canadian Paediatric Society (1994). "Oral Rehydration Therapy and Early Refeeding in the Management of Childhood Gastroenteritis". The Canadian Journal of Paediatrics 1 (5): 160–164. 
  10. ^ Vyas, KS; Wong, LK (2013). "Oral rehydration solutions for burn management in the field and underdeveloped regions: a review.". International journal of burns and trauma 3 (3): 130–6. PMID 23875118. 
  11. ^ Victora, CG; Bryce, J; Fontaine, O; Monasch, R (2000). "Reducing deaths from diarrhoea through oral rehydration therapy". Bull World Health Organ 78: 1246. 
  12. ^ "Oral Rehydration Therapy". Rehydration Project. Retrieved 29 October 2014. 
  13. ^ King, Caleb; Glass, Roger; Bresee, Joseph; Duggan, Christopher. "Managing Acute Gastroenteritis Among Children". CDC MMWR Recommendations and Reports. Retrieved 29 October 2014. 
  14. ^ "Oral rehydration salts and solutions and rice-based solutions worldwide manufacturers and suppliers." Rehydration Project website. Accessed 3 January 2014.
  15. ^ "Oral rehydration therapy (ORT) in children." US Department of Health and Human Services. Accessed 1 January 2014.
  16. ^ Oral rehydration salts
  17. ^ Florez, Jesús (1997). Farmacología Humana (in Spanish) (3rd ed.). Barcelona: Masson. p. 842. ISBN 84-458-0613-0. 
  18. ^ , "WHO position paper on Oral Rehydration Salts to reduce mortality from cholera." World Health Organization, Global Task Force on Cholera Control.
  19. ^ "How to Make an Oral Rehydration Salts Drink (ORS)." Wikihow. Accessed 26 February 2011.
  20. ^ Churgay CA, Aftab Z (1 June 2012). "Gastroenteritis in children: part II, prevention and management". Am Fam Physician 85 (11): 1066–70. PMID 22962878. 
  21. ^ "Diarrhoea, Diarrhea, Dehydration, Oral Rehydration, Mother and Child Nutrition, Water, Sanitation, Hygiene - Rehydration Project". rehydrate.org. Retrieved 22 June 2015. 
  22. ^ WHO Diarrhoeal Diseases Programme 1986: Oral rehydration therapies for the treatment of diarrhoea in the home. WHO CDD SER 86.9. A 14 pp. review paper. http://apps.who.int/iris/bitstream/10665/60117/1/WHO_CDD_SER_86.9.pdf
  23. ^ Sanders; et al. (2013). "Excellent can be the enemy of good: the case of diarrhoea management". The Lancet 382 (9889): 307–308. doi:10.1016/S0140-6736(13)61633-5. 
  24. ^ "New formulation of oral rehydration salts (ORS) with reduced osmolarity." UNICEF.
  25. ^ "New ORS." UNICEF. Accessed 16 February 2009.
  26. ^ "Pharmacopoeia library: oral rehydration salts." WHO Accessed 16 February 2009.
  27. ^ "Improved formula for oral rehydration salts to save children's lives". UNICEF. Retrieved 2008-07-15. 
  28. ^ Kim Y, Hahn S, Garner P (2001). "Reduced osmolarity oral rehydration solution for treating dehydration caused by acute diarrhoea in children". Cochrane Database Syst Rev (2): CD002847. doi:10.1002/14651858.CD002847. PMID 11406049. 
  29. ^ a b Murphy C, Hahn S, Volmink J (2004). "Reduced osmolarity oral rehydration solution for treating cholera". Cochrane Database Syst Rev (4): CD003754. doi:10.1002/14651858.CD003754.pub2. PMID 15495063. 
  30. ^ a b Musekiwa A, Volmink J (2011). "Oral rehydration salt solution for treating cholera: ≤ 270 mOsm/L solutions vs ≥ 310 mOsm/L solutions". Cochrane Database Syst Rev (12): CD003754. doi:10.1002/14651858.CD003754.pub3. PMID 22161381. 
  31. ^ Nalin DR, Hirschhorn N, Greenough W 3rd, Fuchs GJ, Cash RA (2 June 2004). "Clinical concerns about reduced osmolarity oral rehydration solution". JAMA 291 (21): 2632–5. doi:10.1001/jama.291.21.2632. PMID 15173156. 
  32. ^ "Oral rehydration salts: production of the new ORS" (PDF). WHO UNICEF. 2006. 
  33. ^ "The selection of fluids and food for home therapy to prevent dehydration from diarrhoea: guidelines for developing a national policy" (PDF). Programme for the Control of Diarrhoeal Diseases. WHO. 1993. 
  34. ^ a b "WHO position paper on oral rehydration salts to reduce mortality from cholera." WHO 2014. Accessed 1 January 2014.
  35. ^ "Pediatric zinc sulfate oral solution" (PDF). WHO. 15 July 2008. 
  36. ^ Victora CG, Bryce J, Fontaine O, Monasch R (2000). "Reducing deaths from diarrhoea through oral rehydration therapy" (PDF). Bull. World Health Organ. 78 (10): 1246–55. PMC 2560623. PMID 11100619. 
  37. ^ "Community health worker training materials for cholera prevention and control." CDC.
  38. ^ National Guidelines for the Management of Severely Malnourished Children in Bangladesh, Institute of Public Health Nutrition, Directorate General of Health Services, Ministry of Health and Family Welfare, Government of the People's Republic of Bangladesh, May 2008, "Step 3. Treat/prevent dehydration" and "Step 4. Correct electrolyte imbalance," pages 21–23 (22-24 in PDF).
  39. ^ Leibovici-Weissman, Y; Neuberger, A; Bitterman, R; et al. (2014). "Antimicrobial drugs for treating cholera.". Cochrane Database of Systematic Reviews. Art. No.: CD008625 (6). doi:10.1002/14651858.CD008625.pub2. 
  40. ^ a b Guyton & Hall 2010.
  41. ^ Guyton & Hall 2010, p. 330.
  42. ^ "Oral rehydration therapy and early refeeding in the management of childhood gastroenteritis." Paediatrics and Child Health, Canadian Paediatric Society, nutrition committee 2006 11(8) p527–531. Accessed 17 February 2009.
  43. ^ a b Guerrant R. L.; et al. (2003). "Cholera, diarrhea, and oral rehydration therapy: triumph and indictment" (PDF). Clinical Infectious Diseases 37 (3): 398–405. doi:10.1086/376619. PMID 12884165. 
  44. ^ Chatterjee HN (June 1957). "Reduction of cholera mortality by the control of bowel symptoms and other complications". Postgrad Med J 33 (380): 278–84. doi:10.1136/pgmj.33.380.278. PMC 2501333. PMID 13431557. 
  45. ^ a b Ruxin JN (October 1994). "Magic bullet: the history of oral rehydration therapy". Med Hist 38 (4): 363–97. doi:10.1017/s0025727300036905. PMC 1036912. PMID 7808099. 
  46. ^ Crane R. K. et al. "The restrictions on possible mechanisms of intestinal transport of sugars." Membrane Transport and Metabolism, proceedings of a symposium held in Prague, August 22 – 27, 1960. Kleinzeller A. and Kotyk A. Czech Academy of Sciences, Prague, 1961, p439– 449.
  47. ^ Hirschhorn, Norbert (1968). "Decrease in net stool output in cholera during intestinal perfusion with glucose-containing solutions". New Eng. J. Med. 279: 176. 
  48. ^ Pierce, Nathaniel (1968). "Effect of intragastric glucose-electrolyte infusion upon water and electrolyte balance in asiatic cholers". Gastroenterology 55: 333. 
  49. ^ Nalin DR, Cash RA, Islam R, Molla M, Phillips RA (August 1968). "Oral maintenance therapy for cholera in adults". Lancet 2 (7564): 370–3. doi:10.1016/S0140-6736(68)90591-6. 
  50. ^ Hirschhorn, N; Cash, RA; Woodward, WE; Spivey, GH (1972). "Oral fluid therapy of Apache children with acute infectious diarrhoea". Lancet 2 (7766): 15–8. doi:10.1016/s0140-6736(72)91277-9. PMID 4113619. [non-primary source needed]
  51. ^ Hirschhorn, Norbert; McCarthy, Brian J.; Ranney, Bobbette; Hirschhorn, Mary Ann; Woodward, Susan T.; Lacapa, Ann; Cash, Richard A.; Woodward, William E.; Weil, William B. (1973). "Ad libitum oral glucose-electrolyte therapy for acute diarrhea in apache children". The Journal of Pediatrics 83 (4): 562–71. doi:10.1016/S0022-3476(73)80215-X. PMID 4581015. [non-primary source needed]
  52. ^ Hirschhorn, N; Denny, KM (1975). "Oral glucose-electrolyte therapy for diarrhea: A means to maintain or improve nutrition?". The American journal of clinical nutrition 28 (2): 189–92. PMID 1054211. [non-primary source needed]
  53. ^ Gawande, Atul (29 July 2013). "SLOW IDEAS, Some innovations spread fast. How do you speed the ones that don't?". The New Yorker. They found that, although boiled water was preferable, contaminated water was better than nothing. 
  54. ^ Oral rehydration therapy / oral rehydration solution, PATH, "PATH is an international nonprofit organization that transforms global health through innovation."
  55. ^ Source: UNICEF.Pneumonia and Diarrhoea: Tackling the Deadliest Diseases for the World’s Poorest Children. New York: UNICEF; 2012.
  56. ^ 1946–2006, sixty years for children (PDF). UNICEF. November 2006. ISBN 92-806-4053-4. 
  57. ^ "Centre for Health and Population Research — 2001 Gates Award for Global Health Recipient." Bill and Melinda Gates Foundation. Accessed 21 February 2009.
  58. ^ "First Pollin prize in pediatric research recognizing developers of revolutionary oral rehydration therapy." NewYork-Presbyterian Hospital Accessed 22 February 2009.
  59. ^ "Prince Mahidol Award 2006." Prince Mahidol Award Foundation. Accessed 22 February 2009.