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Understanding the use of oral rehydration therapy: A narrative review from clinical practice to main recommendations

Abstract Background and Aims Fluid loss due to diarrhea remains a significant cause of mortality among children under the age of 5. Methods Oral rehydration therapy (ORT) is a first‐line therapeutic measure to compensate the volume loss due to diarrhea and vomiting among gastroenteritis patients. Despite adequate knowledge, the practice of ORT is limited, particularly in developing countries. Results Several recommendations are provided regarding the use of ORT to treat hypovolemia, however, the information regarding its adequate usage is restricted within the healthcare centers and professionals. Conclusion This review highlights the importance of providing recommendations regarding the use of ORT. We also discuss the barriers and alternatives that might limit its use.


| INTRODUCTION
Diarrhea is responsible for 7,600,000 deaths, worldwide, among children aged <5 years. 1 Survival of children suffering from hypovolemic shock depends greatly on the promptness of the treatment. Poorly managed cases have been reported with organ damage, acidosis, kidney failure, and death. Diarrhea-associated hypovolemia is the second leading cause of death among the children aged below 5 years. Volume loss is characterized by reduction in the volume of intracellular fluid and is mainly associated with loss of sodium and water. [2][3][4] The words volume depletion (i.e., hypovolemia) and dehydration are often used interchangeably. However, these terms vary in terms of the physiological conditions resulting from different types of fluid loss. Similar to other research practice, 5 we throughout the text these terms will be used interchangeably ( Figure 1).
Oral rehydration therapy (ORT), first introduced in 1960s, 6 is a gold standard for treating fluid loss as a result of acute diarrhea. 7 Oral rehydration solution (ORS) is composed of iso-osmolar glucose electrolyte solution with base and citrate that is administered to treat dehydration and metabolic acidosis. 8,9 The use of ORS has reduced the incidence of associated morbidities and mortalities, however, over the period of past 30 years, its use remains low or unchanged in many regions of the world. 9,10 According to the monography by UNICEF in 2009, the overall use of ORS was reported to be 33% in developing countries, which could also indicate the possibility of increased child mortality due to diarrhea. 1,[11][12][13] Three significant scientific observation contributed chiefly to the development of ORS: (1) requirement of sodium for the absorption of glucose in small intestine and increase in the absorption of sodium following the presence of luminal glucose, (2) enterotoxin of cholera does not decrease fluid and sodium absorption by the action of intracellular cyclic AMP (adenosine monophosphate), and (3) treatment of acute diarrhea in the field during Bangladesh war in 1970. 8 Additionally, later outbreaks of cholera in Peru and Rwanda proved its efficacy. 14 The following variations of ORS are declared by the World Health Organization (WHO).

| Carrier organic solute
In ORS formula suggested by WHO, glucose is used as an organic solvent carrier for sodium transport (Table 1). Although some promising solutions (e.g., zinc, probiotics, glucose polymers, L-isoleucine, dextrose) have shown effective results, 15,16 there are no definitive data for more routine use. 17,18

| Polymer-based formulas
In polymer-based ORS, rice, wheat, and corn are used as starch sources for glucose. Starch is slowly broken down into glucose molecules by amylase in the small intestine. A systematic review showed that polymer-based ORS was more effective in reducing fecal volume and duration of diarrhea in patients with acute cholera-induced diarrhea or other causes than ORS with glucosebased ORs. 19 However, there is insufficient data to show that the polymer-based ORS is superior to the lower osmolality glucosebased ORS.

| CLINICAL MANAGEMENT OF DEHYDRATION
ORT is the preferred treatment for fluid and electrolyte loss due to diarrhea caused by gastroenteritis in children with mild to moderate dehydration. ORT is used to treat gastroenteritisinduced hypovolemia independent of age, causative agent, or initial sodium content. 20  ORT is generally based on the degree of dehydration of the body.

| Evaluation of dehydration
After deciding to initiate fluid therapy, clinical evaluation of the patient's hydration status is necessary, as it determines clinical decisions on the use of ORT in individuals with the following characteristics: • Identify patients who are not dehydrated and can be transferred home using ORT.
• Identify patients with moderate to low dehydration, where ORT is the preferred treatment for resuscitation.
• Identify patients with severe dehydration who need fluid replacement.
Although attempts have been made to distinguish between mild to moderate dehydration (Table 2), it is still difficult to distinguish clinically between the two degrees of dehydration. 25 As a result, experts in the field group these patients and use a similar management approach when symptoms are overlapped, involving a wide range of dehydration (3%-9% volume reduction).

| Lack of water
For patients with diarrhea but without evidence of water deficiency, ORT is used to maintain hydration by replacing stools, as mentioned above. If stool output is minimal, ORS may not be required.
Regardless of the stool removal, age-appropriate nutrition (including breastfeeding) should be continued with supplemental fluids.

Volume loss ≥10%
Maintenance phase: nutrition and fluids should be resumed, and ORT is continued

| Severe dehydration
Severe dehydration is defined as a volume loss of more than 10% which is treated as follows.

| Rehydration phase
Very severe dehydration is a medical emergency and requires IV treatment with a rapid administration of 20 ml/kg body weight with isotonic saline.
As the patient's clinical status stabilizes and his or her level of consciousness returns to normal, treatment can be switched to ORS.

| Maintenance phase
After repletion is completed, nutrition and fluids should be started, and ORT is continued to replace gastrointestinal excretion.

| COMMERCIAL AND STANDARD ORS
For ORT, the WHO standard or marketable ORS that has a concentration of equimolar 1 glucose and sodium with osmolality should be used. ORS available in the market differs in osmolality and sodium concentration (Table 1). All commercial ORS contain 2%-3% carbohydrates, such as glucose, rice, or other grains; this is sufficient to maintain nutritional status in the short term (24-48 h) until osmol overload in the gut is avoided. 33 6 | OTHER REMEDIES FOR DEHYDRATION

| Household drinks and liquids
Common household fluids for children with hypovolemia include gelatin, tea, fruit juice, sports drinks, and nonalcoholic beverages.
These liquids are low in sodium and almost all of them have a higher carbohydrate content and osmolality than standard ORS ( Table 1). As a result, they are not recommended as a standard ORS alternative for resuscitation in children with gastroenteritis, because there are concerns that may cause hyponatremia-induced osmotic diarrhea.
However, a Canadian clinical trial in 6-to 60-month-old children with mild gastroenteritis without clinical signs of dehydration showed that apple juice (diluted 1: 1 with apple juice and water) compared to standard commercial ORS flavored apples are less susceptible to treatment failure (17%-25%). 34 Zinc supplementation should be prescribed for children with diarrhea in developing countries, due to the prevalence of zinc deficiency. [35][36][37] Additionally, usage of zincbased formula is also effective in reducing diarrhea. 38

| IV rehydration
Alternatively, IV fluid therapy, composed of 0.9% sodium chloride (NaCl) is also used extensively for the compensation of fluid loss following gastroenteritis and diarrhea, particularly. 39 44 To it, ORT is also continued.
The WHO recommends the use IV rehydration therapy for 3-6 h in the cases of severe dehydration. 45 Nonetheless, ORT is a costeffective method for non-severe diarrhea emergencies. 46

CONFLICT OF INTEREST
The authors declare no conflict of interest.

DATA AVAILABILITY STATEMENT
The authors confirm that the data supporting the findings of this study are available within the article.

ETHICS STATEMENT
All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional