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Nurses encouraging a patient to drink an Oral Rehydration Solution to combat dehydration caused by cholera.


Oral rehydration therapy (ORT) is a simple, cheap, and effective treatment for dehydration associated with diarrhea, particularly gastroenteritis, such as that caused by cholera or rotavirus. ORT consists of a solution of salts and sugars which is taken by mouth. It is used around the world, but is most important in the developing world, where it saves millions of children a year from death due to diarrhea—the second leading cause of death in children under five.

Definition

The definition of ORT has changed over time, broadening in scope and encompassing a definition of a specific therapy appropriate for rehydration. Initially, in the early 1980s, ORT was defined only as the official solution prescribed by the WHO/UNICEF. It was later changed in 1988 to also encompass recommended home fluids, as it was noted that access to the official preparation was not always readily available. It was amended once again in 1988 to include continued feeding as appropriate management. In 1991, the definition was changed to define ORT as any increase in administered fluids. The final change came in 1993, and is the definition used today, which states that ORT is an increase in administered fluids and continued feeding.

Administration



According to current WHO/UNICEF guidelines, ORT should begin at home with "home fluids" or a home-prepared "sugar and salt" solution at the first sign of diarrhea to prevent dehydration. Feeding should be continued at all times. However, once dehydrated, the regimen should be switched to official preparations of Oral Rehydration Solution (ORS) at the appropriate dosing times to ensure adequate hydration.

During the home-prepared stage, care should be taken to select the proper type of fluid to administer. The fluids given must contain both sugar and salt in the proper amounts. Liquids without both these components must be avoided. Too little or not enough of either can be ineffective and/or detrimental. Liquids without salt can lead to low body salt (hyponatremia) because the diarrheal stool contains salt and must be replenished. Additionally, sugar must also be present in the administered fluid because salt absorption is coupled with sugar in the intestine via the SGLT1 transporter.

Appropriate drinks to administer during the home-prepared stage include official ORS solutions, salted rice water, salted yogurt-based drinks, and vegetable or chicken soup with salt. Clean water should always be used when preparing a solution. Drinks to be avoided include soft drinks, sweetened fruit drinks, sweetened tea, coffee, and medical tea infusions with diuretic effects due to high sugar content and/or caffeine. In addition, drinks with a high concentration (osmolarity) of sugar can worsen diarrhea as they draw water out of the body and into the intestine because of their hypertonicity.

If dehydration ensues even when ORT is begun with a home-prepared solution, if available, a qualified health professional should manage further rehydration with ORS solution to ensure proper electrolyte balance and to facilitate rapid rehydration, and treatment of the underlying cause of dehydration if appropriate.

Availability

By definition, ORT is available anywhere that adequate nutrition is available. ORS, on the other hand, is typically packaged in pre-measured sachets that are ready to be mixed in with water (generally 1L). These are available via commercial manufacturers or supplied by local/regional governments or relief agencies such as UNICEF. In 1996 alone, UNICEF distributed 500 million sachets of ORS to over 60 developing nations. Among the commercial suppliers, many variations in formulations abound and there is no restriction as to what formulation can be marketed as ORS. As such, some vendors include extra sugar or other flavoring to make the product more palatable, popular examples in the US being the various flavors and formulations of Pedialyte.

Where ORS sachets are not available, home-prepared solutions are typically used. Many recipes exist, but most are some easy-to-remember combination of water, sugar, and salt. An example of such is 1 level teaspoon of salt, 8 level teaspoons of sugar, and (optionally) 4 ounces of orange juice; mixed into 1 liter of clean water. If the water source is questionable, it should be boiled for 10 minutes and allowed to cool before mixing the solution.

WHO/UNICEF definition of ORS

Concentrations of ingredients in Reduced Osmolarity ORS
Ingredient g/L Molecule mmol/L
Sodium chloride (NaCl) 2.6 Sodium 75
Glucose, anhydrous (C6H12O6) 13.5 Glucose 75
potassium chloride (KCl) 1.5 Potassium 20
Chloride 65
trisodium citrate, dihydrate Na3C6H5O7•2H2O 2.9 Citrate 10


The WHO and UNICEF jointly maintain the official guidelines for the contents of reduced osmolarity ORS packets. These guidelines are used by manufacturers of commercial ORS packets that are available for purchase and were last updated in 2006. The reduced osmolarity ORS solution has a total osmolarity of 245 mmol/L.

Zinc supplementation

There is an additional recommendation of zinc supplementation for the management of diarrheal disease in addition to ORS, particularly for pediatric patients. For children under five, zinc supplementation significantly reduces the severity and duration of diarrhea and is strongly recommended as a supplement with ORS for dehydrated children. Preparations are available as a zinc sulfate solution for adults, a modified solution for children, and also a tablet form for children.

Switch to reduced osmolarity ORS

In 2003, WHO/UNICEF changed the ORS formula to a reduced osmolarity version from what it had been recommending for over two decades prior. This change was in response to numerous studies that showed that the standard ORS formula was ineffective in reducing diarrheal stool output compared to other solutions, including rice water. Additionally, further studies showed that a reduced osmolarity solution not only decreased stool output, but also resulted in less vomiting and fewer unscheduled intraveneous therapy. Although UNICEF certifies reduced osmolarity ORS for all forms of dehydration, at least one study cautions that for high stool output cholera-based diarrhea, reduced osmolarity ORS may not sufficiently replenish electrolyte levels, leading to hyponatremia. Though the actual consequence of this appeared negligible, further study was recommended.

The change reduced the osmolarity of the ORS solution from 311 mmol/L to 245 mmol/L. The ingredients reduced in concentration were glucose and sodium chloride. Potassium and citrate concentrations remained the same. The benefits of the reduced osmolarity ORS are reducing stool volume by about 25%, reducing vomiting by nearly 30%, and reducing the need for unscheduled intraveneous therapy by 33%.

Physiological basis

Fluid from the body is normally pumped into the intestinal lumen during digestion. Since this fluid is typically isosmotic with blood, it contains a high concentration of sodium (approx. 142 mEq/L). A healthy individual will secrete 20-30 grams of sodium per day via intestinal secretions. Nearly all of this is reabsorbed by the intestine, helping to maintain constant sodium levels in the body (homeostasis).

Because there is so much sodium secreted by the intestine, without intervention, heavy continuous diarrhea can be a very dangerous and potentially life-threatening condition within hours. This is because liquid secreted into the intestinal lumen during diarrhea passes through the gut so quickly that very little sodium is reabsorbed, leading to very low sodium levels in the body (severe hyponatremia). This is the motivation for sodium and water replenishment via ORT.

Sodium absorption via the intestine occurs in two stages. The first is at the outermost cells (intestinal epithelial cells) at the surface of the intestinal lumen. Sodium passes into these outermost cells by co-transport facilitated diffusion (symport diffusion) via the SGLT1 protein. From there, sodium is pumped out of the cells (basal side) and into the extracellular space by active transport via the sodium potassium pump.

The co-transport of sodium into the epithelial cells via the SGLT1 protein requires glucose or galactose. Two sodium ions and one molecule of glucose/galactose are transported together across the cell membrane through the SGLT1 protein. Without glucose or galactose present, intestinal sodium will not be absorbed. This is the reason glucose is included in ORS solutions.

History

Prescriptions from the ancient physician Sushruta date back over 2500 years with treatment of acute diarrhea with rice water, coconut juice, and carrot soup. However, this knowledge did not carry over to the Western world, as dehydration was found to be the major cause of death secondary to the 1829 cholera pandemic in Russia and Western Europe. In 1831, William Brooke O'Shaughnessy noted the loss of water and salt in the stool of cholera patients and prescribed intravenous fluid therapy (IV) to compensate. The results were remarkable, as patients who were on the brink of death from dehydration recovered. The mortality rate of cholera dropped from 70% to 40% with the use of hypertonic IV solutions. IV fluid replacement became entrenched as the standard of care for moderate/severe dehydration for over a hundred years. ORT replaced it with the support of several independent key advocates that ultimately convinced the medical community of the efficacy of ORT.

In the late 1950s, ORT was prescribed by Dr. Hemendra Nath Chatterjee in India for cholera patients. Although his findings predate physiological studies, his results failed to gain credibility and recognition because they did not provide scientific controls and detailed analysis. Credit for discovery that in the presence of glucose, sodium and chloride became absorbable during diarrhea (in cholera patients) is typically ascribed to Dr. Robert A. Phillips. However, early attempts to translate this observation into an effective oral rehydration solution failed, due toincorrect solution formula and inadquate methodology.

In the early 1960s, biochemist Robert K. Crane discovered the sodium-glucose cotransport as the mechanism for intestinal glucose absorption. Around the same time, others showed that the intestinal mucosa was not disrupted in cholera, as previously thought. These findings were confirmed in human experiments, where it was first shown that a glucose-saline oral therapy solution administered in quantities matching measured diarrhea volumes was effective in significantly decreasing the necessity for IV fluids by 70-80%. These results helped establish the physiological basis for the use of ORT in clinical medicine.

The events surrounding the Bangladesh Liberation War in 1971 convinced the world of the effectiveness of ORT. As medical teams ran out of intravenous fluids to treat the spreading cholera epidemic, Dr. Dilip Mahalanabis instructed his staff to distribute Oral Rehydration Salts (ORS) to the 350,000 people in refugee camps. Over 3,000 patients with cholera were treated, and the death rate was only 3.6%, compared to the typical 30% seen in intravenous fluid therapy. The fact that ORT was delivered primarily by family members instead of trained staff across such a large population in an emergency fashion was demonstrative proof of the utility of ORT against cholera.

Between 1980 and 2006, ORT decreased the number of wordwide deaths from 5 million a year to 3 million a year. Death from diarrhea was the leading cause of infant mortality in the developing world until ORT was introduced. It is now the second leading cause of mortality for children under 5, accounting for 17% of all deaths, second only to pneumonia, at 19%. Its remarkable success has led to naming the discovery of its underlying physiological basis as "potentially the most important medical advance this century." ORT is part of UNICEF's GOBI program, a low cost program to increase child survival in developing countries, including Growth monitoring, ORT, Breastfeeding, and Immunization. Despite the success and effectiveness of ORT, its uptake has recently slowed and even reversed in some developing countries. This raises concerns for increased mortality from diarrhea and highlights the need for effective community-level behavioral change and global funding and policy.

The individuals and organizations involved in the development of ORT have been recognized widely. The 2001 Gates Award for Global Health was awarded to the Centre for Health and Population Researchmarker for its role in the development of ORT. In 2002, the first Pollin Prize for Pediatric Research was awarded to Dr. Norbert Hirschhorn, Dr. Dilip Mahalanabis, Dr. David Nalin, and Dr. Nathaniel F. Pierce for their contributions in the discovery and implementation of ORT. For promoting the use of ORT, the 2006 Prince Mahidol Award was awarded to Dr. Richard Alan Cash, Dr. David Nalin, and Dr. Dilip Mahalanabis in the field of public health; and to Dr. Stanley G Schultz in the field of medicine.

References

  1. Robert K. Crane, D. Miller and I. Bihler. “The restrictions on possible mechanisms of intestinal transport of sugars”. In: Membrane Transport and Metabolism. Proceedings of a Symposium held in Prague, August 22–27, 1960. Edited by A. Kleinzeller and A. Kotyk. Czech Academy of Sciences, Prague, 1961, pp. 439-449.



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