Oral rehydration therapy
|Oral rehydration therapy|
A person with cholera drinking oral rehydration solution (ORS)
Oral rehydration therapy (ORT) is a fluid replacement strategy used to prevent or treat dehydration, most commonly that caused by diarrhea. It involves drinking water with modest amounts of sugar and salt added, while continuing to eat. When diarrhea is severe or long-lasting, the 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.
Vomiting seldom prevents successful rehydration since much of the fluid is still absorbed. If the patient 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.
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. It is on WHO's List of Essential Medicines, a list of the most important medication needed in a basic health system.
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. 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.
In situations where an oral rehydration solution (ORS) is not available, homemade solutions are sometimes used. However, there is currently insufficient evidence to recommend usage of these homemade solutions.
- 1 Medical uses
- 2 Contraindications
- 3 Preparation
- 4 Administration
- 5 Associated therapies
- 6 Physiological basis
- 7 History
- 8 Awards
- 9 Controversy and ongoing investigations
- 10 Sources
- 11 References
Oral rehydration therapy is a treatment for the symptoms of dehydration. 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.
ORT in combination with anti-nausea drugs is indicated for vomiting patients as a strategy to be able to take fluid orally. In an emergency department setting, vomiting, dehydrated patients take these drugs as soon as possible to enable taking fluid by mouth sooner.
Persons taking ORT should eat within 6 hours and return to their full diet within 24–48 hours.
ORT may lower the mortality rate of diarrhea by as much as 93%. Case studies in 4 developing countries also demonstrated the association between increase use of ORT and reduction in mortality.
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 level of dehydration. People who have severe degree of dehydration should seek professional medical help immediately and receive intravenous rehydration as soon as possible to replenish fluid volume in the body.
ORT is contraindicated in the case of protracted vomiting despite proper administration of ORT, worsening diarrhea in excess of fluid intake, onset of stupor or coma, or intestinal blockage (ileus). ORT might also be contraindicated in people who are in hemodynamic shock due to impaired airway protective reflexes. 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 person avoid vomiting.
WHO and UNICEF jointly maintain official guidelines for the manufacture of ORS and recommend various 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 the fluid.
WHO/UNICEF's formula is 2.6 grams (0.092 oz) salt (NaCl), 2.9 grams (0.10 oz) trisodium citrate dihydrate C
2O, 1.5 grams (0.053 oz) KCl, 13.5 grams (0.48 oz) anhydrous glucose C
6 per litre of fluid.
A basic oral rehydration therapy solution is composed of salt and sugar in water, made using a standard ratio and is appropriate for use in situations when ORS must be prepared without the standard ingredients.
- 30 ml sugar : 2.5 ml salt : 1 litre fluid
- 6 level teaspoons sugar : 0.5 teaspoon salt : 1 quart fluid (approx. 1 litre)
The Rehydration Project states, "Making the mixture a little too diluted (with more than 1 litre of clean water) is not harmful."
The optimal fluid is plain, clean water. However, fluids such as rice water, coconut water, vegetable broth, yogurt, weak unsweetened tea, unsweetened fresh fruit juice or even nonpotable water are recommended when plain, clean water is unavailable. Water can be boiled or treated with chlorine. However, ORS is not withheld on the basis of potentially unsafe water. Rehydration takes precedence.
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 litre (34 US fl oz) water. The British Columbia health service suggests sugar free fruit juice mixed with water in a ratio of 1:4.
WHO have in addition to the benefits of ORS, discussed challenges with availability of e.g. packets or suitable teaspoons in poor homes and recommended home made gruels etc. should be considered too. In e.g. 2007, availability of ORS in shops in the main Nairobi slum area was a problem, and use was in decline for various reasons. Likewise in a Lancet 2013 review, due to the stagnant use of ORS, the need was emphasised for more reliable research in rehydration with appropriate home made fluids. See also the introduction.
Low-osmolarity oral rehydration salts
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. This 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.
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.(Section 4.2)
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. In the case of vomiting, WHO recommends a pause of 5–10 minutes, then continuing to slowly administer the fluid. In the case of diarrhea, 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. ORT is often given by parents or other family members in a home setting. ORT is also given by aid workers and health care workers in refugee camps, health clinics and hospital settings.
Mothers should remain with their children if at all possible. WHO recommends continuing breastfeeding and perhaps even re-lactating if circumstances realistically allow.
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.
Continuing to feed the patient, when some appetite is present, speeds the recovery of normal intestinal function, as well as supporting continued nutrition 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), in which case 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 therefore recommended that all severely malnourished children be treated with broad-spectrum antibiotics on admission.
WHO 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.
Feeding should usually resume within 2–3 hours of starting rehydration, and food should be given every 2–3 hours, day and night. 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 fed 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 should be eating 200 ml per kilogram of body weight per 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.
Furthermore, adding antibiotics to the treatment of cholera has been shown to reduce the volume loss due to diarrhea by 50%, and as a result, people require less ORT.
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 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 a life-threatening hyponatraemia within hours. This is the motivation for sodium and water replenishment in ORT.
Sodium absorption occurs in two stages. The first is via intestinal epithelial cells. 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 membrane into the extracellular space.
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 (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.
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".
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 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 1957 Indian physician Hemendra Nath Chatterjee published his results of treating cholera patients 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, biochemist Robert K. Crane 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 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. It was demonstrated 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. Wide application of the therapy in both clinical and non-clinical settings resulted. From that work, Hirschhorn established the clinical physiology of rehydration in children.
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.
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, assuming that the women's numbers would protect them from the supervisor and the supervisor would protect them from others. After visiting with women in the village, each evening they got together and talked about what worked and what did not. They hit upon the method of encouraging the women in the village to making 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 salt packets developed. 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.
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.
- 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
In Rwanda, a charity supplied the sports drink Gatorade, which is not compliant with 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."
- Guyton, A.C.; Hall, J.E. (19 July 2010). Guyton and Hall Textbook of Medical Physiology: Enhanced E-book. Philadelphia: Elsevier Health Sciences. p. 840. ISBN 0-7216-0240-1.
- "The treatment of diarrhea, a manual for physicians and other senior health workers." World Health Organization, 2005.
- "WHO Model List of EssentialMedicines" (PDF). World Health Organization. October 2013. Retrieved 22 April 2014.
- Gerline, A. (8 October 2006). "A simple solution". Time.
- "Water with sugar and salt". Lancet 312 (8084): 300–1. August 1978. doi:10.1016/S0140-6736(78)91698-7.
- The state of the world's children: child survival (PDF). UNICEF. December 2007. p. 8. ISBN 978-92-806-4191-2.
- 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.
- 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.
- 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.
- American College of Emergency Physicians, "Five Things Physicians and Patients Should Question", Choosing Wisely: an initiative of the ABIM Foundation (American College of Emergency Physicians), retrieved January 24, 2014, which cites Hartling, Lisa; Bellemare, Steven; Wiebe, Natasha; Russell, Kelly F; Klassen, Terry P; Craig, William Raine; Craig, William Raine (2006). "Oral versus intravenous rehydration for treating dehydration due to gastroenteritis in children". doi:10.1002/14651858.CD004390.pub2.
- 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.
- Munos, MK; Walker, CL; Black, RE (2010). "The effect of oral rehydration solution and recommended home fluids on diarrhoea mortality". Int J Epidemiol 39 (Suppl 1): i75.
- Victora, CG; Bryce, J; Fontaine, O; Monasch, R (2000). "Reducing deaths from diarrhoea through oral rehydration therapy". Bull World Health Organ 78: 1246.
- "Oral Rehydration Therapy". Rehydration Project. Retrieved 29 October 2014.
- King, Caleb; Glass, Roger; Bresee, Joseph; Duggan, Christopher. "Managing Acute Gastroenteritis Among Children". CDC MMWR Recommendations and Reports. Retrieved 29 October 2014.
- "Oral rehydration salts and solutions and rice-based solutions worldwide manufacturers and suppliers." Rehydration Project website. Accessed 3 January 2014.
- "Oral rehydration therapy (ORT) in children." US Department of Health and Human Services. Accessed 1 January 2014.
- Oral rehydration salts
- , "WHO position paper on Oral Rehydration Salts to reduce mortality from cholera." World Health Organization, Global Task Force on Cholera Control.
- "How to Make an Oral Rehydration Salts Drink (ORS)." Wikihow. Accessed 26 February 2011.
- Rehydration Project
- Churgay CA, Aftab Z (1 June 2012). "Gastroenteritis in children: part II, prevention and management". Am Fam Physician 85 (11): 1066–70. PMID 22962878.
- "Dehydration, treatments and drugs." Mayo Clinic. Accessed 1 January 2014.
- "Oral rehydration therapy." Parent education and resources, British Columbia Guidelines, Canada. Accessed 1 January 2014.
- 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
- Olson et al. 2007: http://www.researchgate.net/publication/51855487_Community_case_management_of_childhood_diarrhea_in_a_setting_with_declining_use_of_oral_rehydration_therapy_findings_from_cross-sectional_studies_among_primary_household_caregivers_Kenya_2007
- Sanders et al. 2013: Excellent can be the enemy of good: the case of diarrhoea management. The Lancet, Volume 382, Issue 9889, Pages 307 - 308. Accessed October 2014: doi:10.1016/S0140-6736(13)61633-5
- "New formulation of oral rehydration salts (ORS) with reduced osmolarity." UNICEF.
- "New ORS." UNICEF. Accessed 16 February 2009.
- "Pharmacopoeia library: oral rehydration salts." WHO Accessed 16 February 2009.
- "Improved formula for oral rehydration salts to save children's lives". UNICEF. Retrieved 2008-07-15.
- 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.
- 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.
- 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.
- "Oral rehydration salts: production of the new ORS" (PDF). WHO UNICEF. 2006.
- "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.
- "WHO position paper on oral rehydration salts to reduce mortality from cholera." WHO 2014. Accessed 1 January 2014.
- "Pediatric zinc sulfate oral solution" (PDF). WHO. 15 July 2008.
- 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.
- "Community health worker training materials for cholera prevention and control." CDC.
- 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).
- 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.
- Guyton & Hall 2010.
- Guyton & Hall 2010, p. 330.
- "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.
- Guerrant R. L. et al."Cholera, diarrhea, and oral rehydration therapy: triumph and indictment." Clinical Infectious Diseases, Infectious Diseases Society of America 2003, vol 37(3) p398 -405. PMID 12884165. Accessed 2 January 2014 and at "Oxford Journals".
- 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.
- 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.
- 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.
- 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.
- 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]
- 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]
- 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]
- 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.
- Oral rehydration therapy / oral rehydration solution, PATH, "PATH is an international nonprofit organization that transforms global health through innovation."
- Source: UNICEF.Pneumonia and Diarrhoea: Tackling the Deadliest Diseases for the World’s Poorest Children. New York: UNICEF; 2012.
- 1946–2006, sixty years for children (PDF). UNICEF. November 2006. ISBN 92-806-4053-4.
- "Centre for Health and Population Research — 2001 Gates Award for Global Health Recipient." Bill and Melinda Gates Foundation. Accessed 21 February 2009.
- "First Pollin prize in pediatric research recognizing developers of revolutionary oral rehydration therapy." NewYork-Presbyterian Hospital Accessed 22 February 2009.
- "Prince Mahidol Award 2006." Prince Mahidol Award Foundation. Accessed 22 February 2009.
- 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.
- "UNICEF: new formulation of oral rehydration salts (ORS) with reduced osmolarity." dead url December 2012.
- Pendergrast, Mark (2010). Inside the Outbreaks: The Elite Medical Detectives of the Epidemic Intelligence Service. Houghton Mifflin Harcourt. pp. 289–91. ISBN 0-547-48723-1.
- Johnson, S.M. (24 December 1994). "AmeriCares relief reached Rwanda first". New York Times.