Scientific Basis of ORS-Composition,Low Osmolarity,Rice Based ORS,Glucose

4th Pediatric Infectious Diseases Conference

ISSN 0973 - 0958

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Oral Rehydration Therapy

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Results

ORAL REHYDRATION THERAPY

Related topics

History and Background

Pathophysiology and Physiology of Diarrhea

Role of ORT in Clinical Management

Swati Kolpuru,
Fellow- Pediatric GI, University of Maryland, USA

Address for Correspondence:

Dr Swati Kolpuru, Pediatric GI Department, University of Maryland, USA. Email: skgupta29@hotmail.com

Scientific basis for ORS (Figure 1)

The intestinal brush-border membrane protein that plays a major part in the absorption of D-glucose from the diet is the Na+/glucose cotransporter (SGLT1). This transporter plays a major role in salt and water absorption, and provides the basis for ORT used to combat diarrhea.

Glucose is absorbed by a 2 stage process

1. Active accumulation across the brush border membrane by SGLT1
2. Downhill transport of glucose out of the enterocyte into the blood across the basolateral membrane by a facilitated glucose transporter (GLUT2).

The sodium gradient across the brush border is maintained by the basolateral Na+K+ pump; that is, the Na+ that enters the cell across the brush border long with sugar is pumped our across the basolateral membrane. The net result is that glucose and salt are absorbed.

The activation of SGLT1 has several other consequences. One involves the contraction of the perijunctional actin-myosin ring, which increases tight junctional permeability and facilitates paracellular transport of water and other small molecules. Activation of SGLT1 also appears to stimulate Na+ H+ pump activity, further enhancing Na+ absorptive capacity of the gut³.

In contrast with other Na+-absorptive pathways, glucose and amino acid stimulated Na+ absorption are not affected by enterotoxins such as cholera toxin and STa (heat-stable enterotoxin of E. coli). This property is the rationale for using sugar or amino acid based oral rehydration solutions (ORS) for the treatment of cholera and traveler's diarrhea⁴.

Rice-based electrolyte solutions also have been effective, because rice starch is rapidly converted to glucose by pancreatic amylase and brush border hydrolases.ORS has saved millions of lives and is highly cost-effective. Similarly, this is the basis for sports drinks, which essentially are sugar-based electrolyte solutions.

Desired composition of ORS

The desired properties for ORS as recommended by the World Health Organization (WHO) and UNICEF for global use include:

Total osmolality between 200 to 310 mmol/L
Equimolar concentrations of glucose and sodium
Glucose concentration not in excess of 20 g/L (111 mmol/L)
Sodium concentration between 60 to 90 meq/L
Potassium concentration between 15 to 25 meq/L
Citrate concentration between 8 to 12 mmol/L
Chloride concentration between 50 to 80 meq/L

This ORS formula can safely be used for all age groups and all etiologies of diarrhea. ORS replaces the lost fluid and electrolytes and maintains fluid and electrolytes. Maximum uptake of water and electrolytes occurs when the ratio of carbohydrates to sodium in these solutions approaches one, but formulas range from ratios of 1:1 to 2:1⁵. Beverages with high sugar content (eg, fruit juices and soda) with a molar ratio of glucose in excess of sodium will increase diarrheal losses. The higher unabsorbed glucose load will increase the osmolality in the lumen, decreasing water absorption. Other fluids with excess sodium concentration compared with glucose (eg, chicken broth) also will increase diarrheal losses, as there is no organic solute for facilitated transport of sodium. Fluids with high sodium concentration also may result in hypernatremia. Potassium and chloride in the formula replace those lost in the stool of patients with diarrhea. Citrate, a base precursor, corrects acidosis and enhances the absorption of water and electrolyte. The ORS formula has changed very little in the last decade except that sodium bicarbonate has been replaced by trisodium citrate, a more stable compound which allows for longer storage and cheaper packaging⁶.

Low osmolarity ORS

Oral rehydration solutions have been improved since the early days: the formula was adjusted after a Cochrane Library systematic review in 2001 showed that a less concentrated solution had better outcomes⁷.
The need for unscheduled supplemental IV therapy in children given this solution was reduced by 33%. In a combined analysis of this study and studies with other reduced osmolarity ORS solutions (osmolarity 210- 268 mOsm/l, sodium 50-75 mEq/l) stool output was also reduced by about 20% and the incidence of vomiting by about 30%. The 245 mOsm/l solution also appeared to be as safe and at least as effective as standard ORS for use in children with cholera.
This new formula replaces the original ORS, and is the only ORS used globally by the WHO.(see Table 1)

Table 1: Composition of new ORS

New ORS	grams/litre	%	New ORS	mmo/litre
Sodium chloride	2.6	12.683	Sodium	75
Glucose, anhydrous	13.5	65.854	Chloride	65
Potassium chloride	1.5	7.317	Glucose, anhydrous	75
Trisodium citrate, dihydrate	2.9	14.146	Potassium	20
			Citrate	10
Total	20.5	100.00	Total Osmolarity	245

Rice based ORS

Rice powder, being mostly starch, releases more than twice the amount of glucose when digested than is present in standard ORS solution. This is enough glucose to support both the absorption of water and electrolytes in the ORS solution and the reabsorption of a portion of the water and electrolytes secreted into the bowel as part of the diarrheal process. Protein in the rice powder may add to this effect through the release and absorption of amino acids. The osmotic activity of rice-ORS solution (about 220 mOsm/l) is lower than that of blood or other tissues (about 290 mOsm/l).

The results of the clinical trials performed to date indicate that the rate of stool loss is significantly reduced in patients with acute diarrhea given rice-ORS solution as compared with patients given glucose-ORS solution and it also reduces the duration of diarrhea.

Rice based ORS is recommended in patients with cholera. Future studies are needed to assess the effect of rice based ORS in children with acute, non-cholera diarrhea.