The traditional method for treating acute dehydration caused by diarrhea is the administration of fluids intravenously, or by venoclysis. By providing direct access to the bloodstream, this method allows precise control over the amounts of fluid, electrolytes, medicines and, often, nutrients that a patient receives.
But it presents formidable drawbacks. To begin with, the procedure requires sterile conditions and highly skilled personnel. In many countries, only physicians are legally allowed to administer intravenous treatments. The materials themselves, including fluid bottles and infusion equipment, are costly, difficult to transport and often must be imported. Careful supervision is required, and the patient must remain essentially immobile.
In short, intravenous therapy is a hospital procedure. And despite the usual precautions, iatrogenic septicemic infections caused by faulty intravenous technique are distressingly frequent in many hospitals in developing countries.
Nowhere were these limitations more evident than in South Asia during the advance of the seventh global cholera pandemic through Bangladesh, India and Pakistan in the 1960s. Cholera is the most feared and severe of all diarrheal diseases. Evacuation rates in acute adult cases characteristically exceed 10 liters per day, and fatality rates in untreated cases may be higher than 50%.
Faced with the impossibility of applying classical parenteral treatments to the thousands of cases produced by the epidemic, desperate clinicians unearthed an old but forgotten form of treatment: oral rehydration therapy.
As early as 1949, it had been shown that a solution of glucose and electrolytes administered orally could successfully rehydrate children with acute diarrhea. At that time, however, the physiological basis of oral rehydration was not well understood. In any case, the method went unnoticed in the face of traditional medical wisdom regarding antidiarrheal therapy, namely, that the intestine cannot absorb during acute diarrhea and must be allowed to “rest” until the diarrhea stops.
During the 1950s, several fundamental in vitro studies helped clarify the mechanism by which the intestine absorbs water and certain electrolytes. The key observation was that sodium ions, which are lost during acute diarrhea, are absorbed by the intestine in the presence of glucose, and that this mechanism of “active transport” in turn stimulates the passive absorption of water.
Researchers also observed that this absorption mechanism remains intact despite acute cholera infection. These observations were confirmed in subsequent clinical trials, many of them carried out by heroic cholera researchers in South Asia.
Moreover, it was found that the losses of three other fundamental electrolytes during acute cholera — chloride, potassium and bicarbonate — could be replaced simply by adding them to the oral formula.
By 1970, comprehensive trials carried out in the main cholera treatment centers had demonstrated that oral rehydration therapy was inexpensive and easy to administer, and that it could reduce the need for intravenous fluids by 70% or more.
Other clinical studies soon showed that oral rehydration was equally effective in treating non-cholera diarrheas in all age groups. This was an important finding because electrolyte losses vary considerably between cholera and non-cholera diarrhea, and between adults and children.
Despite these variations in stool losses and the different pathological mechanisms of a wide variety of diarrheal agents, researchers found that almost all cases of acute diarrhea could be successfully treated using the same basic oral solution.
In 1971, WHO approved the use of the following glucose and electrolyte formula for the treatment of acute diarrhea in all ages, regardless of etiology.
At the same time, progress in research in other disciplines, particularly epidemiology, microbiology and immunology, greatly expanded knowledge of diarrheal diseases and allowed other valuable advances. Among these was the recognition of new and important diarrhea-causing organisms, especially rotavirus and enterotoxigenic Escherichia coli, as well as the development of the effective enzyme-linked immunosorbent assay, or ELISA, which has considerably simplified the diagnosis of common enteropathogenic germs.
