A Controlled Trial of Bismuth Subsalicylate in Infants with Acute Watery Diarrheal Disease

Background: Bismuth subsalicylate is a common constituent of over-the-counter medications for diarrhea. However, it is uncertain whether bismuth offers any more benefit than standard oral rehydration therapy with early feeding. Methods: We conducted a placebo-controlled, randomized trial to evaluate the effect of bismuth subsalicylate (100 or 150 mg per kilogram of body weight per day for up to 5 days) on the duration and volume of acute watery diarrhea in 275 male infants and young boys (mean age, 13.5 months). Serum salicylate and bismuth levels were monitored throughout the study and were also measured two weeks after discharge. All the patients received fluid replacement by the oral route and early feeding of easily digestible foods with high caloric density. Results: Diarrhea stopped within 120 hours of admission in 74 percent of the patients given placebo, 89 percent of those given 100 mg of bismuth per kilogram (P = 0.009 vs. the placebo group), and 88 percent of those given 150 mg of bismuth per kilogram (P = 0.019 vs. the placebo group). As compared with the patients given placebo, those given bismuth had significant reductions in their total stool output (P = 0.015), total intake of oral rehydration solution (P = 0.013), and duration of hospitalization (P = 0.005); there was no significant difference between the two groups given bismuth in these clinical outcomes. All measurements of bismuth and salicylate concentrations in blood were well below concentrations considered toxic. No adverse reactions were seen. Conclusions: Treatment with bismuth subsalicylate decreases the duration of diarrhea and is a safe and effective adjunct to oral rehydration therapy for infants and young children with acute watery diarrhea., Bismuth subsalicylate has been in common use in the United States for more than 75 years as an over-the-counter treatment for diarrhea,¹ but only recently have its efficacy and safety been assessed through controlled clinical trials. Controlled studies indicate that this treatment is effective and prevents traveler's diarrhea². DuPont et al.³ showed that bismuth subsalicylate reduced the frequency of unformed stools, increased stool consistency, and decreased the frequency of nausea and abdominal cramps in American students residing in Mexico. Steinhoff et al.⁴ found bismuth to have a beneficial effect when given for viral gastroenteritis due to Norwalk agent. Bismuth…