Richard Fiddian-Green raises interesting questions about the possible direct effects of proton pump inhibitors on the colon. Although we hypothesized that the use of proton pump inhibitors increases patients' risk by making them more susceptible once exposed or perhaps through effects on the intestinal flora,1 we questioned the possibility of other mechanisms, especially given that proton pumps in the colon have been described. Diarrhea is in fact one of the more common side effects of proton pump inhibitors.2 The reports of lansoprazole-induced microscopic colitis3 and the possible effects of elevated gastrin levels from use of proton pump inhibitors in the colon,4 as well as the hypothesis raised by Fiddian-Green regarding increased ischemic risk for the intestinal mucosa, suggest that research in this area is warranted.
In some of the more severe cases we have observed, we questioned whether progression to a more fulminant course occurred because of a combination of an infectious with an ischemic insult, with the following possible scenario: severe diarrhea from C. difficile causes dehydration and relative hypotension, which leads to either global or localized bowel ischemia, which then acts as a motor for a systemic inflammatory response syndrome and a more fulminant presentation. The possibility that the reverse occurs — prior relative intestinal ischemia leading to increased susceptibility to the toxin and a more severe presentation — is intriguing, especially in light of a report by Dallal and associates.5 These authors found that cardiothoracic procedures and vascular surgery were the most common operations that preceded fulminant C. difficile colitis, although this observation may simply reflect the high rate of these procedures.
I believe that the current outbreak is primarily infectious, since the observation of bloody diarrhea has been the exception rather than the rule; nonetheless, the contribution of an ischemic insult should be considered in the more severe forms. At this point, many unanswered questions remain, but hopefully continued research in this area will help clinicians to decrease the incidence of infection and improve patient outcomes.
Sandra Dial Departments of Critical Care and Respirology McGill University Montréal, Que.
Footnotes
Competing interests: None declared.
References
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