History and rationale of oral rehydration and recent developments in formulating an optimal solution

Oral rehydration therapy with glucose-electrolyte solutions has been one of the major therapeutic advances of the century. This alarmingly simple intervention developed from a basic scientific observation in the laboratory, when it was shown that sodium and glucose transport in the small intestine are coupled and thus the presence of glucose in an electrolyte solution promotes absorption of both sodium ions and water. Even more important, sodium/glucose co-transport continues despite the secretory diarrhoea of cholera and enterotoxigenic E. coli and after intestinal damage due to rotavirus. Despite widespread use of the oral rehydration solutions (ORS) recommended by the World Health Organization (WHO), controversy continues about the optimal composition of these solutions. Discussion centres around the sodium and glucose concentrations, the osmolality and whether base (bicarbonate) or base-precursor (citrate) is necessary. Already there is a clear divide between the developing world, where the WHO solution (Na 90, glucose 111 and bicarbonate 30 mmol/L) is widely used, and the industrialised world, where solutions with lower sodium and until recently higher glucose concentrations have been favoured. Recently, attempts have been made to optimise ORS using animal and human model systems before submitting new candidate ORS to clinical trial. Results to date suggest that hypotonic ORS containing 50-60 mmol/L sodium and 90-100 mmol/L glucose produce maximal water absorption. The presence of base or base-precursor appears to offer little with regard to the promotion of sodium and water absorption and its role in combating acidosis remains controversial. Complex substrates such as rice powder and glucose polymers may eventually replace glucose in ORS, since their addition reduces ORS osmolality still further.