Correspondence
Amylase-Resistant Starch plus Oral Rehydration Solution for Cholera
N Engl J Med 2000; 342:1995-1996June 29, 2000
- Article
To the Editor:
Ramakrishna et al. (Feb. 3 issue)1 report that the inclusion of amylase-resistant starch in an oral rehydration solution improved the treatment of cholera by reducing stool output and the duration of diarrhea. The comparison groups received standard glucose-based oral rehydration solution with or without the addition of rice flour. We believe the design of this small study and the interpretation of its results were both inappropriate. There is no rationale for adding rice flour to standard glucose-based oral rehydration solution, nor are there reports on the use of such a solution, which contains considerably more organic solute and has a much higher osmolality than conventional rice-based oral rehydration solution. The patients in the study who received oral rehydration solution with rice flour added to it should be considered a second experimental group. Standard glucose-based oral rehydration solution was the only true control in the trial, but prior experience with conventional rice-based oral rehydration solution is also relevant.
In the four reported trials of rice-based oral rehydration solution for the treatment of adults with cholera, stool output in the first 24 hours was 24 to 41 percent lower in the group of patients who received rice-based oral rehydration solution than in the group of patients who received glucose-based oral rehydration solution.2 In contrast, the study by Ramakrishna et al. showed only an 8 percent reduction in stool output in the first 24 hours with the use of oral rehydration solution containing glucose plus rice flour and only a 14 percent reduction with oral rehydration solution containing glucose plus amylase-resistant starch, as compared with standard oral rehydration solution with glucose. Contrary to the authors' interpretation, these results strongly suggest that glucose-based oral rehydration solution with rice flour or amylase-resistant starch added is appreciably less effective than standard rice-based oral rehydration solution, at least during the first 24 hours, when the stool output was greatest. The authors note that much of the reported benefit of amylase-resistant starch occurred in the second 24 hours of treatment, whereas rice-based oral rehydration solution reduces stool output throughout treatment. This finding suggests that the beneficial effect of amylase-resistant starch is delayed. However, this effect is likely to be considerably reduced when effective antimicrobial therapy is given at the outset, as is universally recommended. Such treatment routinely reduces stool output during the second 24 hours by about 65 percent, as compared with no antibiotic treatment, and causes diarrhea to end within 48 hours.3
We believe that oral rehydration solution containing amylase-resistant starch deserves further study as a treatment in adults with cholera. To determine whether amylase-resistant starch is effective and can increase the efficacy of rice-based oral rehydration solution, an appropriately designed study might compare three formulations: conventional rice-based oral rehydration solution, oral rehydration solution containing amylase-resistant starch as the only organic solute, and oral rehydration solution containing both rice and amylase-resistant starch with all patients receiving immediate treatment with an effective antimicrobial agent. Such a study should be performed before extending this research to include the treatment of children with acute diarrhea from causes other than cholera, in whom rice-based oral rehydration solution has no advantage over standard glucose-based oral rehydration solution.4
4 ReferencesNathaniel F. Pierce, M.D.
Johns Hopkins University School of Hygiene and Public Health, Baltimore, MD 21205Olivier Fontaine, M.D.
World Health Organization, 1211 Geneva, SwitzerlandR. Bradley Sack, M.D., Sc.D.
Johns Hopkins University School of Hygiene and Public Health, Baltimore, MD 212051
Ramakrishna BS ,Venkataraman S ,Srinivasan P ,Dash P ,Young GP ,Binder HJ . Amylase-resistant starch plus oral rehydration solution for cholera. N Engl J Med 2000;342:308-313
Full Text | Web of Science | Medline2
Gore SM ,Fontaine O ,Pierce NF . Impact of rice based oral rehydration solution on stool output and duration of diarrhoea: meta-analysis of 13 clinical trials. BMJ 1992;304:287-291
CrossRef | Web of Science | Medline3
Alam NH ,Majumder RN ,Fuchs GJ . Efficacy and safety of oral rehydration solution with reduced osmolality in adults with cholera: a randomised double-blind clinical trial: CHOICE study group. Lancet 1999;354:296-299
CrossRef | Web of Science | Medline4
Gore SM ,Fontaine O ,Pierce NF . Efficacy of rice-based oral rehydration. Lancet 1996;348:193-194
CrossRef | Web of Science | Medline
Author/Editor Response
The authors reply:
To the Editor: We appreciate the comments of Dr. Pierce and his colleagues. Our hypothesis was that the inclusion of amylase-resistant starch, a substrate targeted at colonic absorption because of its metabolism to short-chain fatty acids, would improve the efficacy of oral rehydration solution with regard to the reduction of both fecal volume and the duration of diarrhea. The first issue raised by Pierce et al. concerns our choice of control groups, which were patients who received glucose-based oral rehydration solution and those who received glucose-based oral rehydration solution with rice flour added; a rice-based diet was provided to both groups, and patients were encouraged to eat as soon as possible. The purpose of adding rice flour to standard oral rehydration solution was not to evaluate rice-based oral rehydration solution but instead to serve as a control for the added carbohydrate load in the patients receiving amylase-resistant starch. As we explained, neither rice flour nor maize starch increased the osmolality of the oral rehydration solution.
The second issue concerns the efficacy of our interventions as compared with efficacy in studies of rice-based oral rehydration solution.1 All the patients in our study (including the control group that received glucose-based oral rehydration solution) received rice-based food immediately after initial rehydration. Although the reduction in fecal volume is greater with rice-based oral rehydration solution than with glucose-based oral rehydration solution,1 the provision of a normal rice-based diet to patients with cholera will by itself reduce fecal volume.2 This may well explain why the addition of rice flour or amylase-resistant starch to oral rehydration solution did not reduce fecal volume in the first 24 hours as much as did the treatment in the cited studies, most of which were performed before early feeding became routine practice in the management of cholera. Alternatively, since amylase-resistant starch should increase fluid absorption in the colon but not in the small intestine, the delay in its efficacy may be related to the more distal site of its action.
Finally, although the administration of doxycycline after 24 hours (rather than at the time of admission) may in part explain the more prolonged diarrhea in our patients, other investigators have delayed or withheld antibiotic treatment in patients with cholera.3
We agree with Pierce et al. that additional clinical trials are required to establish the optimal formulation of amylase-resistant starch as an adjuvant to oral rehydration solution.
3 ReferencesB.S. Ramakrishna, M.D., Ph.D.
Christian Medical College, Vellore, IndiaHenry J. Binder, M.D.
Yale University, New Haven, CT 065201
Gore SM ,Fontaine O ,Pierce NF . Impact of rice based oral rehydration solution on stool output and duration of diarrhoea: meta-analysis of 13 clinical trials. BMJ 1992;304:287-291
CrossRef | Web of Science | Medline2
Molla AM ,Molla A ,Rohde J ,Greenough WB III . Turning off the diarrhea: the role of food and ORS. J Pediatr Gastroenterol Nutr 1989;8:81-84
CrossRef | Web of Science | Medline3
Patra FC ,Majumder RN ,Eeckels R ,Desjeux JF ,Mahalanabis D . Sacolene in cholera: a double blind randomized controlled trial. Scand J Infect Dis 1999;31:151-154
CrossRef | Web of Science | Medline
- Citing Articles (2)
Citing Articles
1
A. Atia, A. L. Buchman. (2010) Treatment of cholera-like diarrhoea with oral rehydration. Annals of Tropical Medicine and Parasitology 104:6, 465-474
CrossRef2
J. H. Hoekstra, H. Szajewska, M. Abu Zikri, D. Micetic-Turk, Z. Weizman, A. Papadopoulou, A. Guarino, J. A. Dias, B. Oostvogels. (2004) Oral Rehydration Solution Containing a Mixture of Non-Digestible Carbohydrates in the Treatment of Acute Diarrhea: A Multicenter Randomized Placebo Controlled Study on Behalf of the ESPGHAN Working Group on Intestinal Infections. Journal of Pediatric Gastroenterology and Nutrition 39:3, 239-245
CrossRef
