Abstract
Question Recently, I had a visit from a 5-year-old patient who had been given bismuth subsalicylate for a diarrheal illness by a local family physician during a trip to South America. Is this a practice we should encourage?
Answer Research from developing countries has found the use of bismuth subsalicylate to be effective in shortening the duration of diarrheal illness. Despite these findings, its limited effectiveness and concerns about it potentially causing Reye syndrome, compliance, and cost are the key reasons it is not routinely recommended for children.
Bismuth salicylate is a derivative of salicylic acid, hence its potential anti-inflammatory and antibactericidal action. Bismuth subsalicylate (which has various trade names) is a colloidal substance obtained by hydrolysis of bismuth salicylate.
Bismuth subsalicylate in combination with zinc salts has been a known treatment for diarrhea since the early 1900s, and it was used to treat sick infants, mostly suffering from cholera.1 Some studies suggest that bismuth subsalicylate inhibits intestinal secretion caused by enterotoxigenic Escherichia coli and cholera toxins.2 This finding gained support in one study that found that bismuth subsalicylate was associated with clearance of pathogenic E coli from the stools of 100% of treated children but was not associated with rotavirus elimination.3
Randomized controlled trials
In 1993 the New England Journal of Medicine published the results of a randomized placebo-controlled trial examining 275 Peruvian boys (mean age 13.5 months) who were given bismuth subsalicylate (100 or 150 mg/kg of body weight per day for up to 5 days) together with oral rehydration therapy. Duration of diarrheal illness was significantly shorter among those receiving bismuth subsalicylate (either dose) compared with those receiving placebo (P = .019, P = .009), measured as diarrhea resolution at 120 hours after admission. The number of patients that needed to be treated was 7 to 8. Furthermore, total stool output (P = .015), total intake of oral rehydration solution (P = .013), and duration of hospitalization (P = .005) were also shorter for treated children.4
In another double-blind, placebo-controlled study from Chile,3 a dose of 20 mg/kg of bismuth subsalicylate was given 5 times daily for 5 days as an adjunct to rehydration therapy in 123 children 4 to 28 months of age who had acute diarrheal illness that was severe enough to necessitate hospitalization. The investigators reported a substantial reduction in duration of hospital stay when children were given bismuth subsalicylate (total stay of 6.9 days) compared with patients receiving placebo (8.5 days). The investigators also found a substantial decrease in stool frequency and stool weight, as well as an improvement in stool consistency, improved clinical well-being, and shortening of the disease duration.
A third double-blind randomized controlled study from Bangladesh assessed children 4 to 36 months of age with acute diarrhea.5 A dose of 100 mg/kg daily of liquid bismuth subsalicylate for 5 days resulted in a milder and shorter duration of illness compared with those treated with placebo, although this difference was not significant (P = .057).
In all studies,3–5 bismuth subsalicylate was well tolerated with no reported adverse effects, and when serum salicylate and bismuth levels were measured, there was no evidence of toxicity found for any dose given.
Further considerations
Although evidence from trials seems to show the benefit of bismuth subsalicylate in diarrhea, especially in developing countries, several concerns have been raised. In 1993, Snyder discussed the issue of the cost of bismuth subsalicylate products.6 While prices have changed over time, there is no current study about the cost-effectiveness of bismuth subsalicylate products to suggest if developing countries should consider their wide use.
Other concerns expressed by the American Academy of Pediatrics7 include insufficient data to assess the risk of Reye syndrome in children receiving salicylate therapy, as well as the potential lack of compliance with a medication given every 5 hours for 5 days. Finally, a very benign but surprising side effect of bismuth subsalicylate includes black discoloration of the tongue8 and melena.9
Conclusion
Studies conducted in developing countries found the use of bismuth subsalicylate for diarrhea was effective in shortening the duration of illness; however, despite these findings, potential risks of Reye syndrome and compliance challenges inhibit recommendations to use bismuth subsalicylate in children with diarrhea.
Notes
PRETx
Child Health Update is produced by the Pediatric Research in Emergency Therapeutics (PRETx) program (www.pretx.org) at the BC Children’s Hospital in Vancouver, BC. Dr Goldman is Director of the PRETx program. The mission of the PRETx program is to promote child health through evidence-based research in therapeutics in pediatric emergency medicine.
Do you have questions about the effects of drugs, chemicals, radiation, or infections in children? We invite you to submit them to the PRETx program by fax at 604 875-2414; they will be addressed in future Child Health Updates. Published Child Health Updates are available on the Canadian Family Physician website (www.cfp.ca).
Footnotes
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Cet article se trouve aussi en français à la page 845.
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Competing interests
None declared
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