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Clonidine Reduces Diarrhea, Sodium Loss
Alan Buchman, MD, MSPH, FACN, FACP, FACG, AGAF
The following article heavily reprints material from the discussion section of Buchman AL, Fryer J, Wallin A, Ahn CW, Polensky S, Zaremba K., "Clonidine reduces diarrhea and sodium loss in patients with proximal jejunostomy: a controlled study.” Journal of Parenteral and Enteral Nutrition, 2006;30:487–491, with permission from the American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.).
For patients with short bowel syndrome, fluid management is a significant problem. It is possibly even more of a problem than absorption of adequate calories and protein. Fluid management is especially difficult for patients with minimal remaining intestine. In a study, investigators found they could decrease the amount of diarrhea and sodium loss in the stool of these patients by approximately 10 percent using a clonidine skin patch. While this is a modest decrease, taken from the perspective of patients who have maximized other antidiarrheal therapies, and if used in conjunction with other antidiarrheal therapies, it is clinically significant.
Just like old buildings, some old drugs may have new uses. Clonidine is a medication traditionally used to treat high blood pressure. It has also been used effectively in treating diarrhea in patients with diabetes, and in animal and human studies it has been shown to have significant antimotility effects and to prolong intestinal transit time. A prolonged transit time allows the absorptive surface of the intestine to have increased contact time with nutrients and fluids, which may allow for greater absorption. Further, in a previous study of patients with cholera, clonidine decreased fecal sodium and potassium losses.
This study was undertaken to see if clonidine could increase fluid absorption for PN-dependent patients who had very little intestine that ended in a proximal jejunostomy. Maintaining adequate hydration is especially difficult for these patients. The study was also designed to measure fecal sodium and potassium losses.
For this controlled, unblinded study, eight PN-dependent subjects received clonidine transdermally, in the form of the skin patch Catapres. All of the patients received their usual antimotility agents, including diphenoxylate, loperamide hydrochloride, or codeine (none used octreotide), and seven of them drank oral rehydration solutions. Lacking any remaining colon, these eight patients all had difficulty managing fluids, and dietary adjustments had little effect on them.
Clonidine was administered transdermally because, in addition to malabsorption of nutrients and fluids, patients with short bowel syndrome often have difficulty absorbing medication. The transdermal route also ensures continuous delivery. The clinical practice of the investigators is to encourage multiple meals and snacks in this patient population, although some foods may interfere with the absorption of certain medications.
The study results showed a 9 percent decrease in fecal wet weight in patients, as well as a decrease in fecal sodium loss. Although this decrease is relatively modest, it is clinically significant in patients for whom alternative antidiarrheal therapy has been maximized.
The decrease in fluid losses with clonidine therapy was similar to the decrease in fluid requirements demonstrated with growth hormone in populations with in-continuity colon. When extrapolated over a full week, clonidine reduced losses 3.0 L/week and growth hormone 2.1 L/week, once decreases related to dietary intervention are subtracted. The observations of a 9 percent reduction per day were in patients without residual colon, in whom fluid management is much more difficult and dietary adjustments have little to no effect.
The reason for the decrease in fecal fluid loss is not entirely clear, and in this pilot study, no attempt was made to wean PN fluid volume. However, PN fluid volume can be reduced if a daily urine volume of >1200 mL is sustained.
Although with clonidine therapy investigators observed a significant decline in fecal sodium loss along with fecal fluid loss, no relationship was found between residual bowel length and fecal sodium loss. There was no effect on fecal potassium loss. Despite the decrease in fecal sodium loss, all end jejunostomy patients had a sodium excretion substantially greater than dietary sodium intake. Thus, such patients always require significant parenteral sodium infusion.
It is unclear from the results whether the decrease in loss was a result of increased jejunal sodium absorption or a decrease in sodium secretion. Experimental studies with animals have shown clonidine enhances sodium absorption. Sodium is actively absorbed in the jejunum, and a strong correlation has been observed between sodium absorption and water absorption.
Given the role of the colon in sodium absorption in patients with short bowel syndrome, it is possible clonidine would be even more effective in patients with some in-continuity colon. Further, the lower dose of transdermal clonidine was selected (0.3 mg./week) for the study because this was the first study and the investigators were concerned about the potential of patients developing low blood pressure (none did). Quite possibly a larger dose, such as 0.6 mg./week, might exhibit greater efficacy.
Transdermal clonidine is pharmacologically available and can now be considered a potential therapy in patients with short bowel syndrome and high fluid losses. However, long-term data will be needed to determine whether the effects are sustained over long time periods.
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