A spoonful of sugar...

Cholera epidemics have been a major public health issue throughout recorded history and much energy was devoted towards preventing them and treating affected patients once they occurred. However, it was not until 1831 that it was recognized that the deaths were due to a loss of both salt and water in the stool. At the same time, it was shown that salt and water alone orally or by enemas was ineffective and potentially harmful and iv fluids were introduced for the treatment of cholera for the first time. Despite this, mortality remained very high and as late as 1906, 40% of infected patients still died. Intravenous fluids remained the mainstay of treatment for diarrheal infections until the 1970s.

Although the Indian physician Sushruta had described using solutions containing rice water and carrot juice to treat diarrhea more than 3000 years ago, these had not been in vogue in the West. In the 1960s, small scale studies were done showing that oral solutions containing salt alone were not absorbed but that if the salt was combined with glucose, absorption of both was enhanced. This led to an increase in the use of oral rehydration therapy through the 1960s although it was not fully accepted as a replacement for iv fluids at that point. The first major use of ORT was in a camp for Bangladeshi refugees in 1971. The doctors ran out of iv fluids and ORT was used to treat more than 3000 patients with mortality falling from 30% to 3.6%.

So why is ORT so effective in the treatment of diarrhea in general and especially cholera? The cholera toxin binds irreversibly to the luminal membrane of the small intestine leading to activation of protein kinase A and ultimately increasing the number of open Cl channels on the luminal membrane. The exodus of Cl is accompanied by loss of Na through the tight junctions between the cells and so patients can become dehydrated very rapidly. ORT works because of the particulars of glucose absorption in the small intestine. The glucose transporter SGLT1 requires 2 Na in order to absorb one glucose molecule. ORT contains equimolar amounts of Na and glucose. Thus, the absorption of 100mmol of glucose requires the absorption of 200mmols of NaCl. The second 100mmols of NaCl comes from intestinal secretions and this amount is equivalent to about 700mls of isotonic secreted fluids. Thus, not only does ORT provide rehydration itself, but it also actually decreases diarrhea volume and reduces the requirement for iv fluids.

This was one of the major public health advances of the 20^th century and has significantly reduced mortality from diarrheal illnesses worldwide. ORT solutions are cheap and widely available and, most importantly, are easy to administer with no training. Knowing your electrolyte transport mechanisms is important.

This is a great review of the past and future of ORT and this is a previous post by Nate comparing ORT and Gatorade.