Oral Rehydration Solution

Oral rehydration therapy
Intervention
MeSH eMedicine 906999-treatment

Oral rehydration therapy is the use of modest amounts of sugar and salt added to water in order to prevent and/or treat dehydration. This dehydration is most commonly caused by diarrhea. Dehydration can also be caused by vomiting. Even in cases of vomiting, the person or caretaker can pause for five to ten minutes, and then give ORS (oral rehydration solution) more slowly. Much of the fluid is still absorbed, and vomiting usually subsides after the first hour or two.[1]

The World Health Organization (WHO) recommends a wide variety of common household recipes and drinks which can be used to prevent and treat dehydration: unsalted rice water, salted rice water, unsalted vegetable broth, salted vegetable broth, weak tea, green coconut water, yogurt drink, etc. Plain water can also be given. WHO emphasizes starting early in order to hopefully prevent dehydration.[1]

For moderate to severe dehydration, there are medically prepared and medically recommended packets which can be added to water. Such packets vary in composition, but usually contain a mixture of glucose, sodium, potassium, and citrate. These are often used in conjunction with, or instead of, intravenous fluid replacement. For homemade solutions, authorities have differing recommendations, whether it should be 1 liter (34 oz) water, 6 teaspoons sugar, 1 teaspoon salt ("taste of tears")---or whether it should only 1/2 teaspoon salt.[2] Even different WHO publications have differing recommendations.[3] The Rehydration project states, "Making the mixture a little too diluted (with more than 1 litre of clean water) is not harmful."[4]

As part of oral rehydration therapy, WHO recommends supplemental zinc (10 to 20 mg daily) for 14 days, which will help to reduce the severity and duration of this diarrheal episode, as well as making future diarrhea less likely in the following two to three months. WHO also recommends continuing to feed the person with diarrhea as this will help speed recovery of normal intestinal function. And the child will gain some nutrients from the food, making malnutrition less likely. In the specific case of a child with some dehydration, he or she should not be fed during an initial four hour rehydration period, except for breastmilk. Children on a rehydration plan longer than four hours should be given food every three or four hours. Even children with diarrhea can usually absorb sufficient nutrients from food to support continued growth and weight gain. Children whose dehydration have been corrected should be fed before being sent home in order to emphasize to the parents and other family members the importance of continuing to feed a child with diarrhea. Most children with watery diarrhea regain their appetite as soon as their dehydration is corrected. Children with bloody diarrhea often eat poorly until the illness resolves, and these children should be encouraged to resume normal feeding as soon as possible. Children often tolerate frequent small feedings better than infrequent larger feedings.[1][5] In the specific case of cholera, the United States' CDC (2010) recommends that adults and children with diarhhea should continue to eat, and that children who are breastfed should continue to be breastfed.[6]

ORT is effective in treating fluid loss after acute diarrhea due to various causes, such as dysentery and gastroenteritis, including that brought on by cholera or rotavirus. Many studies, including those conducted by the World Health Organization, have shown that ORT dramatically reduces the number of deaths experienced during and after epidemics of cholera. ORT is considered to be one of the most relevant public health advances of the 20th century.[7]

Definition

The definition of ORT has changed over time, broadening to include a definition of a specific therapy appropriate for rehydration. Initially, in the early 1980s, ORT was defined only as the solution prescribed by the WHO/UNICEF. It later changed in 1988 to encompass recommended home fluids, because the official preparation was not always readily available. It was amended again in 1988 to include continued feeding as appropriate management. In 1991, the definition changed to define ORT as an increase in administered hydrational fluids. The final change came in 1993—the definition used today—which states that ORT is an increase in administered fluids and continued feeding.[7][5]

WHO/UNICEF definition of ORS

Concentrations of ingredients in reduced osmolarity ORS[8]
Ingredient g/L mmol/L
sodium chloride (NaCl) 2.6 75
glucose, anhydrous (C6H12O6) 13.5 75
potassium chloride (KCl) 1.5 20
trisodium citrate, dihydrate
Na3C6H5O7·2H2O
2.9 10

updated recipe[9]

Basic solution

A basic oral rehydration therapy solution is composed primarily of salt, sugar, and water using a standard ratio[7][10][11] - e.g.

  • 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[12] 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.[13] The reduced osmolarity ORS has a total osmolarity of 245 mmol/L.[8]

Switch to reduced osmolarity ORS

In 2003, WHO/UNICEF changed the ORS formula to a reduced osmolarity version from what it had recommended for more than two decades.[8] 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.[14][15][16][17][18] Additionally, further studies showed that a reduced osmolarity solution not only decreased stool output, but also resulted in less vomiting and fewer unscheduled intravenous therapy cases.[19][20][21] Although UNICEF certifies reduced osmolarity ORS for all forms of dehydration,[8] 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.[22][23]

The change reduced the osmolarity of the ORS 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.[8] The benefits of the reduced osmolarity ORS are reducing stool volume by about 25 percent, reducing vomiting by nearly 30 percent,[24] and reducing the need for unscheduled intravenous therapy by 33 percent.[25]

Administration

See also Management of dehydration.

Current WHO/UNICEF guidelines,[26] recommend that 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.[27] The fluids given must contain both sugar and salt in the proper amounts. Liquids without salt can lead to low body salt (hyponatremia) because the diarrheal stool contains salt that must be replenished, although too much salt (hypernatraemia) should be avoided as well. Additionally, sugar must also be present in the administered fluid because salt absorption is coupled with sugar in the intestine via the SGLT1 transporter,[27] although once again drinks with too much sugar, such as 'soft drinks,' should be avoided as these can draw water from the body into the gut.[1]

A baby can be given rehydration solution by using a dropper or a syringe without the needle. Children under two can be given a teaspoon every one to two minutes. Older children and adults can take frequent sips directly from a cup. Vomiting often occurs during the first hour or two of rehydration treatment, but this seldom prevents successful rehydration since most of the fluid is still absorbed. If the patient vomits, wait five to ten minutes, and then start giving ORS again, just more slowly. For example, a child under two can be given a teaspoonful every two to three minutes.[1]

WHO (2005) recommends a child with some dehydration, except for breastmilk, not being given food during the initial four hour rehydration. Children on a rehydration plan longer than four hours should be given food every three or four hours. Even children with diarrhea can usually absorb sufficient nutrients from food to support continued growth and weight gain. Children whose dehydration have been corrected should be fed before being sent home in order to emphasize to the parents and other family members the importance of continuing to feed a child with diarrhea. Most children with watery diarrhea regain their appetite as soon as their dehydration is corrected. Children with bloody diarrhea often eat poorly until the illness resolves, and these children should be encouraged to resume normal feeding as soon as possible. Children often tolerate frequent small feedings better.[1] In addition, continuing to feed the adult or child patient with diarrhea also speeds recovery of normal intestinal function.[1][5] The United States' CDC (2010) recommends, in the specific case of cholera, that adults and children with diarhhea should continue to eat, and that children who are breastfed should continue to be breastfed.[6]

In the book Inside the Outbreaks: The Elite Medical Detectives of the Epidemic Intelligence Service, the author writes regarding Rwanda, “One misguided charity had sent Gatorade, which caregivers gave to the dying children, only making them worse,” presumably because Gatorade is too rich and makes dehydration worse.[28] At a CDC-sponsored continuing education program on "Surviving Field Stress For First Responders" (2005), a panel participant who is an on-scene coordinator with the Emergency Response Branch EPA recommended, “You also want to think about the balance of what you're drinking and maintain a proper electrolyte balance. You should drink one half water and one half sports drink on site during responses. Don't drink just one or the other.”[29]

Appropriate treatments include official ORSs, salted rice water, salted yogurt-based drinks, and vegetable or chicken soup with salt. Clean water should always be used if possible when preparing a solution. In the case of cholera, CDC states, "If no fuel is available for boiling water or if no chlorine products are available to treat water to make it safe, community members should still make ORS with the water they have because ORS with any water can save lives."[6] And presumably this may apply to other cases of severe diarrhea. Drinks with diuretic properties (due to high sugar content and/or caffeine) should be avoided. Drinks with a high concentration (osmolarity) of sugar, such as soft drinks and commercial fruit drinks, can worsen diarrhea as they draw water out of the body and into the intestine because of their hypertonicity.[27]

Availability

The World Health Organizations states that some home products can be used to treat and prevent dehydration. This includes salted rice water, salted yogurt drink, and salted vegetable or chicken soup. A home-made solution of one litre of plain water with 3 grams table salt (one level half teaspoonful) and 18 grams common sugar (three teaspoons) can also be made. And a medium amount of salt can also be added to water in which cereal has been cooked, unsalted soup, green coconut water, unsweetened weak tea, and unsweetened fruit juice.[1] The homemade solution should have the "taste of tears."[3] If available, supplemental zinc and potassium can be added to or given with the homemade solution.[1]

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[30] or supplied by local/regional governments or relief agencies such as UNICEF. In 1996, UNICEF distributed 500 million sachets of ORS to over 60 developing nations.[31] Commercial suppliers produce a variety of formulations, 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 Drip Drop ORS, Frutolyte, H2ORS, and Pedialyte.

Scheduled to start in October 2011,[dated info] there is a pilot program in Zambia that will test to what extent piggybacking ORS and zinc on Coca-Cola's distribution channels could improve access to these medicines, particularly in rural areas. The project, called Colalife uses the empty spaces in crated bottles of Coke to supply wedge-shaped packets of medicine that contain oral rehydration salts.[32]

Food and supplements

An adult or child with diarrhea should continue to eat, and infants should continue to breast-feed.[1][6] In a 2005 publication for doctors regarding the treatment of diarrhea, the World Health Organization states: "When food is given, sufficient nutrients are usually absorbed to support continued growth and weight gain. Continued feeding also speeds the recovery of normal intestinal function, including the ability to digest and absorb various nutrients. In contrast, children whose food is restricted or diluted lose weight, have diarrhea of longer duration, and recover intestinal function more slowly".[1]

Zinc supplementation[33] is recommended to manage 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.[25] Preparations are available as a zinc sulfate solution for adults,[34] a modified solution for children,[35] and also a tablet form for children.[36]

Treatment when malnourished

Dehydration may be overestimated in a marasmic/wasted child and underestimated in a kwashiorkor/edematous child. The diagnosis is based instead on whether the person has been having diarrhea.[1][37] Rehydration Solution for Malnutrition (ReSoMal) contains less salt and more sugar and potassium than regular ORS.[37] In addition, the World Health Organization recommends that all malnourished individuals with diarrhea be treated with a course of broad-spectrum antibiotics.[1] Supplemental zinc is still recommended, and a dehydrated person should still continue to be given food.[1]

Physiological basis

Fluid from the body is normally pumped into the intestinal lumen during digestion. This fluid is typically isosmotic with blood because 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).[38]

Because there is so much sodium secreted by the intestine, without intervention, heavy continuous diarrhea can become a potentially life-threatening condition within hours. This is because liquid secreted into the intestinal lumen during diarrhea passes through the gut so quickly that little sodium is reabsorbed, leading to dangerously low sodium levels in the body (severe hyponatremia).[38] 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 via the SGLT1 protein.[38] From there, sodium is pumped out of the cells (basal side) and into the extracellular space by active transport via the sodium potassium pump.[39][40]

The Na+/K+ ATPase pump on the basolateral membrane of the proximal tubule cell uses ATP to move 3 sodium outward into the blood, while bringing in 2 potassium. This creates a downhill sodium gradient inside the proximal tubule cell in comparison to both the blood and the tubule.

The SGLT proteins use the energy from this downhill sodium gradient created by the ATPase pump to transport glucose across the apical membrane against an uphill glucose gradient. Therefore, these co-transporters are an example of secondary active transport. (The GLUT uniporters then transport the glucose across the basolateral membrane, into the peritubular capillaries.) 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 the epithelial cells via the SGLT1 protein requires sodium. Two sodium ions and one molecule of glucose/galactose are transported together across the cell membrane through the SGLT1 protein. Without sodium present, intestinal glucose or galactose will not be absorbed. This is why ORSs include both sodium and glucose. For each cycle of the transport, hundreds of water molecules move into the epithelial cell, slowly rehydrating the affected individual.[38]

History

Over 2,500 years ago, Indian physician Sushruta described the treatment of acute diarrhea with rice water, coconut juice, and carrot soup.[41] This treatment was not known in the Western world, and 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) 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 percent to 40 percent with the use of hypertonic IV solutions.[42] 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.[43]

In the late 1950s, ORT was prescribed by Dr. Hemendra Nath Chatterjee in India for patients diagnosed with cholera.[44] Although his findings predate physiological studies, his results failed to gain credibility and recognition because they did not provide scientific controls and detailed analysis.[43] 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. Early attempts to create an effective oral rehydration solution based on this observation failed, due to incorrect solution formula and inadequate methodology.[43]

In the early 1960s, biochemist Robert K. Crane discovered the sodium-glucose cotransport as the mechanism for intestinal glucose absorption.[45] 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 80 percent.[46] These results helped establish the physiological basis for the use of ORT in clinical medicine.[42]

The events surrounding the Bangladesh Liberation War in 1971 convinced the world of the effectiveness of ORT.[43] 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 percent, compared with the typical 30 percent seen in intravenous fluid therapy.[42] 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.[43]

Between 1980 and 2006, ORT decreased the number of deaths that occurred worldwide from 5 million a year to 3 million a year.[47] Death from diarrhea was the leading cause of infant mortality in the developing world until ORT was introduced.[48] It is now the second leading cause of mortality for children under five, accounting for 17 percent of all deaths, second only to pneumonia, at 19 percent.[49] Its remarkable success has led to naming the discovery of its underlying physiological basis as "potentially the most important medical advance [of the 20th] century."[48] 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.[50] 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.[51]

The individuals and organizations involved in the development of ORT have received wide recognition. The 2001 Gates Award for Global Health was awarded to the Centre for Health and Population Research, located in Dhaka, Bangladesh, for its role in the development of ORT.[52] 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.[53] For promoting the use of ORT, the 2006 Prince Mahidol Award was awarded to Dr. Richard A. Cash of Harvard School of Public Health, Dr. David Nalin of Albany Medical College, and Dr. Dilip Mahalanabis in the field of public health; and to Dr. Stanley G. Schultz in the field of medicine.[54]

Controversy and ongoing investigations

A 2004 "Clinician's Corner" article in the Journal of the American Medical Association criticized the then new reduced-osmolarity formula as not providing enough sodium for adults with cholera. This article recommends different solutions for such patients beginning in controlled settings such as cholera treatment centers and hospitals.[55]

See also

References

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