Glucose Amino acids Oligopeptides

FIG. 2. Mechanism of solute-coupled sodium co-transport in the enterocyte.

1%. Use of the WHO-ORS has been promoted widely throughout the developing world with a major decline in morbidity and mortality from acute diarrhoeal disease. ORT is safe and effective in neonates and in all except those with most severe degrees of dehydration. Clinical trials clearly show that ORT can correct both hypernatraemia and hyponatraemia and can successfully reverse acidosis in neonates and young infants.

Current controversies in ORT. The major controversies over the composition of ORS centre around the sodium and glucose concentrations and thus, osmolality, to which these components are the major contributors. Debate continues as to the necessity for including a base (bicarbonate) or base-precursor (citrate) in ORS, particularly as many other forms of metabolic acidosis such as diabetic ketoacidosis, are managed successfully by the administration of base-free fluids (Elliott et al 1987). Finally, although glucose has traditionally been the main substrate for ORS, the possibility that efficacy might be increased by using complex substrates such as cereals, resistant starch or defined glucose polymers continues to be discussed and may play an increasingly important role in future ORS formulations.

Sodium. The sodium concentration of ORS needs to be high enough to replace sodium losses and correct hyponatraemia but not so high as to cause or worsen hypernatraemia, which can itself occasionally result in death. The sodium concentration of the WHO-ORS, 90mmol/l was probably derived from the faecal sodium concentration in adults with cholera (Molla et al 1981). Concern about widespread use of the 90 mmol/l ORS relates to hypernatraemia and periorbital oedema which occasionally occur with WHO-ORS in infants and children in the developed world fed on high solute feeds. Concerns about hypernatraemia were particularly evident in the developed world resulting in the proliferation of new ORS formulations with lower sodium concentrations (30— 60 mmol/l). Part of the rationale for these developments was the observation that more than 50% of cases of acute diarrhoea in infants and young children in industrialized countries were due to rotavirus infections in which the stool sodium concentration was much lower than that of cholera. All clinical trials in well-nourished and malnourished children of all ages, including neonates and young infants in developed and developing communities have shown that ORS with sodium concentrations in the 50—60 mmol/l range are safe and effective for rehydration and maintenance therapy of mild to severe dehydration from acute non-cholera diarrhoea (Elliott et al 1989). Thus, in the developing world where bacterial gastroenteritis due to enterotoxigenic E. coli and cholera continues to be important, use of the 90 mmol/l WHO-ORS continues to be recommended for its safety and efficacy. However, with the increasing importance of rotavirus diarrhoea, with its associated lower sodium losses, lower sodium (50—60 mmol/l) ORS are more applicable for use in industrialized countries and are probably safe and effective in the vast majority of geographic locations in the developing world; indeed recent clinical trials would support this view.

Glucose. Glucose was the first substrate shown to be effective for ORTand is the most widely used worldwide. ORS glucose concentrations vary widely between that present in the WHO-ORS (111 mmol/l) to much higher concentrations of 200—300 mmol/l found in some of the early ORS that were produced commercially for used in industrialized countries. Recent studies in animal models of secretory diarrhoea have shown that reducing glucose concentration below that found in the WHO-ORS, does not significantly reduce glucose or sodium absorption and has in addition an important contribution by increasing water absorption, related at least in part to the lower osmolality of these solutions (Hunt et al 1991,Thillainayagam et al 1998). Recent clinical studies confirm that low glucose (70—100 mmol/l), hypotonic ORS reduce stool volume in children with acute gastroenteritis (Rautanen et al 1993, International Study Group on Reduced-Osmolality ORS solutions 1995).

ORS osmolality andcomplexsubstrates. Until several years ago, the WHO-ORS and the majority of commercially available ORS were isotonic or moderately hypertonic, because of the relatively high concentrations of sodium and/or glucose. There is now evidence that high glucose ORS may increase stool volume, because of monosaccharide intolerance, and high sodium ORS, particularly if administered without ad libitum water in the maintenance phase, can produce hypernatraemia.

The discovery that rice powder and other cereals could replace glucose and improve efficacy of ORT in the early 1980s had an important impact on our thinking, both regarding the physiological principles of ORT and also its practical implementation (Gore et al 1992, Thillainayagam et al 1998). One important aspect of these solutions is that it is possible to deliver an increased amount of substrate without increasing the overall osmolality, because glucose is present in the form of starch, a high molecular weight molecule. It has been difficult to demonstrate increased substrate absorption in human disease states and studies in animal models have failed to show that this was the explanation for their increased efficacy. However, it is clear that the osmolality of the cereal-based solutions is extremely low, usually in the range of 150—170 mOsm/kg.

In recent years, we and others examined the hypothesis that reducing ORS osmolality is the major determinant for improving water absorption from both simple and complex carbohydrate-based ORS. We were able to show that reducing osmolality of standard glucose—electrolyte ORS resulted in improved water absorption in all of the models described. The majority of ORS now used in the UK are hypotonic (Table 3). Thus, these studies with complex carbohydrate ORS and the previous work with low osmolality glucose ORS suggest that osmolality is an important determinant of ORS efficacy (Thillainayagam et al 1998).

Rice/starch based ORS has been shown to be superior to WHO-ORS in adults with cholera and in infants with acute diarrhoea, the majority of whom had rotavirus infection. The major benefit accrued from these ORS relates to reduced faecal losses because of increased absorption of fluid and electrolytes.

The concept of using complex carbohydrate in ORS has recently been developed further with the incorporation ofamylase-resistant starch in place ofglucose or rice starch (Ramakrishna et al 2000). Resistant starch, such as that found in certain varieties of high-amylose maize starch, is poorly digested in the small intestine such that 50—70% of this starch passes into the colon and is fermented to short chain fatty acids (SCFAs). SCFAs promote sodium and fluid absorption in the colon and therefore might enhance the pro-absorptive capacity of ORS. This proposal has been evaluated in a randomized controlled trial in cholera which compared WHO-ORS with rice starch ORS and a resistant starch ORS. The resistant starch ORS significantly reduced faecal losses and the duration of the diarrhoea compared to the other two ORS. It remains to be established whether

TABLE 3 Composition (mmol/1) of oral rehydration solutions available in the UK in 2000

Osmolality

ORA Na K Cl HCO3 Citrate Glucose (calculated)

Powders

Oral rehydration salts BP

Powders

Oral rehydration salts BP

WHO

90

20

80

10

111

311

Diocalm Junior

60

20

50

10

111

251

Dioralyte

60

25

45

20

90

240

Dioralyte Relief

60

20

50

10

_+

Electrolade

50

20

40

30

111

251

Rehidrat

50

20

50

20

9

91*

336

Effervescent tablets

Dioralyte

60

25

45

20

90

240

Data from British NationalVorrnulary, March 1999. +Contains cooked rice powder 6 g/sachet (30 g/l). *Also contains sucrose 94mmol/l and fructose 1—2 mmol/l.

Data from British NationalVorrnulary, March 1999. +Contains cooked rice powder 6 g/sachet (30 g/l). *Also contains sucrose 94mmol/l and fructose 1—2 mmol/l.

resistant starch ORS is also more effective in other forms of acute infective diarrhoea.

The Sugar Solution

The Sugar Solution

Curb Sugar Cravings Once And For All With These Powerful Techniques. Sugar sensitive people might be low in specific neurochemicals that help us feel calm, centered, confident, and optimistic. Sugar is a drug that temporarily makes the sugar sensitive feel better, but with damaging consequences.

Get My Free Ebook


Post a comment