Rice-based oral rehydration solution decreases the stool volume in acute diarrhoea.

Bulletin ofthe WorldHealth Organization, 63 (4): 751-756 (1985) © World Health Organization 1985 Rice-based oral rehydration solution decreases the stool volume in acute diarrhoea* A. M. MOLLA,' S. M. AHMED,2 & W. B. GREENOUGH III3 A randomized trial using oral rehydration solutions (ORS) with rice or glucose was carried out in 342 patients with acute watery diarrhoea. On admission, 75% of these patients had severe dehydration and 70% werepositivefor Vibrio cholerae. There were 185 children aged under 10 years and 157 adults; 169 patients were treated with rice-ORS and 173 with glucose-ORS. Patients in both groups were comparable in age and body weight, as well as the duration and severity of illness. Patients with severe dehydration were first rehydrated intravenously, and then treated with ORS. Those with moderate dehydration received ORSfrom the beginning. The mean stool output in the first 24 hours in children treated with rice-ORS was less than that in those treated with glucose-ORS (155 vs 204 ml/kg/24 h; P < 0.01). The same was truefor the adult patients, the corresponding values for stool output being 115 vs 159 ml/kg/24h (P < 0.05). The mean ORS intake in children was263.5 vs379.6 ml/kg/24 h, respectively, for rice-ORS andglucose-ORS (P <0.05); the corresponding intakes in adult patients were, respectively, 180.5 and 247 ml/kg/24 h. A gain ofabout 10% ofthe body weight on admission was observed in all the groups. Six cases (4 children and 2 adults), who failed to respond to oral rehydration after intravenous therapy, all belonged to the glucose-ORS group. Oral rehydration therapy is simple and inexpensive, but can be improved further to reduce the cost and provide increased nutrition (1, 2). Thus, less expensive sucrose has been used instead of glucose (3, 4); polymers of glucose (5) and individual amino acids (6) have also been used, and chicken soup with glucose or starch has been suggested (7). Although a sucrose-electrolyte solution is as effective as the glucose-electrolyte solution in treating acute diarrhoea, the osmotic penalty from the presence of these small molecules in the gut lumen imposes a limit to the number of calories that can be given in such solutions. Recently 30 g of rice powder with the recommended electrolytes has been used successfully in oral rehydration solutions (ORS) to treat acute diarrhoea (8). In vivo the hydrolysis of rice by intra- luminal enzymes gradually yields glucose, amino acids and oligopeptides, which enhance sodium absorption through an independent carrier system (9). A study in Calcutta using 50 g of rice powder per litre of ORS not only effectively hydrated patients * From the International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR, B), G.P.O. Box 128, Dhaka-2,* Bangladesh. 1 Paediatric Gastroenterologist, ICDDR, B. Requests for reprints should be sent to this author. 2 Physician, ICDDR, B. 3 Director, ICDDR, B. On deputation to ICDDR, B from the Division of Geographic Medicine, The Johns Hopkins University, Baltimore, ND, USA. with diarrhoea, but also sharply reduced the stool volume (10). The present study tested the maximum quantity of rice that could be made into a drinkable solution (80 g/l), using the same electrolytes as recommended by WHO for oral rehydration therapy in acute diarrhoea (14).' PATIENTS AND METHODS Selection ofpatients The study was carried out in the outpatient ward of the International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR, B), during an epidemic of cholera between December 1982 and March 1983. A total of 342 patients (185 children under 10 years old and 157 adults), having moderate to severe dehydration and a history of diarrhoea of less than 24 hours but without signs of systemic disease, were included in this study; patients who had received ORS or antibiotics before coming to the hospital were excluded. The research protocol had previously been approved by the Ethical Review Committee of the ICDDR, B. Informed consent was obtained from the patients or their guardians. Body a:A manualfor the treatment ofacute diarrhoea. Geneva, World Health Organization, 1980 (unpublished document, WHO/CDD/ SER/80.2). 4580 751- 752 A.M. MOLLA ET AL. weights on admission were measured to the nearest 10 g and each patient was examined and the degree of dehydration assessed. The patients were assigned to one of two treatment groups, glucose-based ORS or rice-based ORS, according to a predetermined random number. The study could not be "blind" because of the obvious difference in the appearance of the two solutions. Rice powder (800 g/10 litres) was packaged separately, the contents being boiled for 5-7 minutes in 10.5 litres of water to produce a colloidal suspension. After cooling, electrolytes were added to the gruel mixture. Rehydration therapy Severely dehydrated patients received intravenous rehydration with Dhaka solution,b and were then assigned to one of the ORS groups. Those with moderate dehydration were placed on oral therapy from the beginning. ORS was fed by the patients' attendants and was supervised by paramedics. The study was designed so as not to change any routine clinical procedures of the ICDDR, B patients, who also received normal feeding ad lib during treatment. Patients positive for Vibrio cholerae by darkfield microscopy and/or culture received tetracycline (500 mg, 6 hourly) after initial rehydration, but children under 10 years old received furazolidone (5 mg/kg body weight, 6 hourly). Measurement of fluid intake and output, every 12 hours, continued during the study period, as did the measurement of pulse, body weight, and blood pressure and assess- b Composition of this solution per litre: sodium, 133 mmol; potassium, 13 mmol; chloride, 98 mmol; acetate, 48 mmol. ment of dehydration. Patients were discharged after they had passed the first formed stool, which usually took 2-3 days. A total of 103 adults (57 in the rice- ORS group and 46 in the glucose-ORS group) were treated with tetracycline, and 141 children (61 in the rice-ORS group and 80 in the glucose-ORS group) were treated with furazolidone. Declaration offailure After starting oral rehydration therapy, patients who were unable to drink because of persistent vomiting, or who failed to make good the fluid losses from purging, were reassessed for severity of dehydration, based on clinical criteria such as pulse rate, blood pressure, body weight and fluid balance. Those who went into negative fluid balance after a second intravenous fluid infusion were considered therapeutic failures. Such patients were discharged from the study, but continued to receive routine diarrhoea care after blood was taken for determining the erythrocyte volume fraction and electrolyte levels. Laboratory examination The study was designed to provide therapy in a busy diarrhoeal diseases treatment centre during a large cholera epidemic. Laboratory investigations and all other measurements were therefore kept to a minimum. Rectal swabs were taken for darkfield examination, and stools were taken for culture in Salmonella-Shigella medium and MacConkey's plates. In cases of therapeutic failure, blood was drawn for erythrocyte volume fraction and electrolyte measurements. Table 1. Comparison of various characteristics of diarrhoeal children treated with rice-ORS and glucose-ORS Rice-ORS° Glucose-ORS' (n = 84) (n= 101) Age (years) 5.2 ±0.28 5.1 ± 0.25 Males/females 52/32 57/44 Body weight on admission (kg) 11.6 ±0.38 12.1 ±0.43 Duration of diarrhoea prior to admission (hours) 14.2 ± 1.4 14.6± 1.4 Dehydration status Mild (%) 0 0 Moderate (%) 25 28 Severe (%) 75 72 Volume of initial intravenous therapy (ml) 956.8 ± 73.6 882.5 ± 61.0 Duration of stay in hospital (hours) 28.9 ± 1 .27 29.8 ± 1.0 Cholera/non-cholera cases 61/23 80/21 a Values are means ± S.E. RICE-BASED ORAL REHYDRATION SOLUTION RESULTS The 342 patients studied included 185 children, 84 of whom were in the rice-ORS group with an age distribution as follows: below 2 years, 8; 2-5 years, 36; and 5-10 years, 40. All the children in each ORS group were analysed together; the same was done with the adults also. Tables 1 and 2 show the general characteristics of both ORS groups before and during therapy. Age, body weight, duration of diarrhoea and degree of dehydration were similar for both adults and children in both the rice- and glucose-ORS groups. Most of the patients (75-85%) presented with severe dehydration, with less than a 24-hour history of diarrhoea; and about 70%o of them were positive for V. cholerae, both by darkfield microscopy and by Table 2. Comparison of various characteristics of adult diarrhoeal patients treated with glucose-ORS and rice-ORS Rice-ORS a (n= 85) Glucose-ORS° (n= 72) Age (years) 24.2 ± 1.2 23.6 ± 1.2 Males/Females 45/40 32/40 Body weight on admission (kg) 34 ± 1.0 34± 1.0 Duration of diarrhoea prior to admission (hours) 13.1 ± 1.2 15.6 ± 2.0 Dehydration status Mild (9) 0 0 Moderate (9%) 14 24 Severe (%) 86 76 Volume of initial intravenous therapy (ml) 2484.7 ± 139.7 2338.6 ± 170.0 Duration of stay in hospital (hours) 28 ±0.94 29.8 ± 1 .4 Cholera/non-cholera cases 57/28 46/26 a Values are means+ S.E. Table 3. Effect of 24- and 48-hour treatment with rice-ORS and glucose-ORS in diarrhoeal children Rice-ORSa Glucose-ORS' P values (n=84) (n= 101) Stool output (ml/kg/24 h) 1st 24 hours 155.2 ± 13.0 (84)b 203.8± 13.9 (101)b < 0.01 2nd 24 hours 124.5 ± 9.0 (14) 235.5 ± 20.3 (16) < 0.05 Total volume (ml/24h) 2089 213.1 2255.8 ± 190.4 < 0.05 Intravenous intake (ml/kg/24 h) 1 st 24 hours 110 11.1 (68) 109.4± 9.4 (84) NS" 2nd 24 hours 0 0 ORS intake (ml/kg/24 h) 1 st 24 hours 263.5 ± 12.3 (84) 379.6 ± 17.0 (101) < 0.05 2nd 24 hours 191.2 11.5 (14) 316.8 ± 17.6 (16) <0.05 % gain in body weight in 1st24hours 10.9±0.75 11.2±0.62 NS a Values are means ± S.E. bFigures in parentheses are the number of patients studied. c NS= not significant. 753 A.M. MOLLA ET AL. Table 4. Effect of 24- and 48-hour treatment with rice-ORS and glucose-ORS in adult diarrhoeal patients Rice-ORSe Glucose-ORS' P vaues(n = 85) (n = 72) Stool output (ml/kg/24 h) 1 st 24 hours 1 15.0 ± 10.1 (85)" 158.7 ± 12.8 (72)1 < 0.05 2nd 24 hours 78.6 ± 9.4 (13) 157.9 ± 14.9 (17) < 0.05 Total volume (ml/24h) 4175 379.8 6115 531.3 < 0.005 Intravenous intake (ml/kg/24 h) 1 st 24 hours 99.1 ±8.0 (74) 94.7 9.1 (58) NS' 2nd 24 hours 0 0 ORS intake (ml/kg/24 h) 1 st 24 hours 180.5 7.6 (85) 247.5 14.2 172) < 0.05 2nd 24 hours 127.6±8.9 (13) 226±13.3(17) < 0.05 % gain in body weight in 1st24hours 10.4±0.6 11.1±0.6 NS a Values are means ± S.E. Figures in parentheses are the number of patients studied. NS = not significant. culture. Any patient having more than one etiology for the diarrhoea was excluded from the study. In 24% of the children and 36%o of the adult patients no enteric pathogen could be isolated by routine culture. Student's t-test was applied to compare the efficacy of the two types of ORS, the results for the children and for adult patients are presented in Tables 3 and 4, respectively. Table 3 shows that children in the rice- ORS group passed less stool and required less ORS, both in the first and second 24 hours of therapy, than did children treated with glucose-ORS. This difference is significant (P< 0.05). Compared with the weight on admission, the patients in both groups, on average, gained more than 107o in body weight after 24 hours of ORS; similar results were obtained with the adult patients, as shown in Table 4. There were six therapeutic failues (as defined above) in the glucose-ORS group; 4 were children, 2 were adults and all were positive for cholera infection. There were no such failures in the rice-ORS group. DISCUSSION This study has shown that, even under epidemic conditions of severe cholera or in cholera-like diarrhoea, the glucose or sucrose component of oral rehydration solutions can be replaced by rice powder with improved results. Glucose and sucrose are manufactured products which are costly and not always available in countries where diarrhoeal diseases are a problem. Rice, a staple food in many of these countries, reduces the fluid requirements when used in ORS and also provides increased nutrition even in the acute stage of illness. The first observation of its efficacy compared with glucose was reported in 1982 (8). Shortly thereafter, rice-ORS was shown to reduce the stool volume (10). When glucose, however, was used at a concentration of more than 20 g/l, the stool volume increased by 15-29% (11, 12); polyglucose in place of glucose caused hypernatraemia (5). Thus, any attempt to provide extra calories in ORS using glucose is exposed to an "osmotic penalty" since these small molecules exert an osmotic force which draws salts and water from the mesenteric circulation into the gut lumen, thus aggravating the dehydration. The comparatively large, osmotically inactive molecules of rice do not present this problem. The osmolarity of rice-ORS containing 80 g rice powder and electrolytes is thus lower (288 milliosmol/l) than that of glucose-ORS (330 milliosmol/l) (13; Molla et al., unpublished observations, 1984). The present study has demon- strated that even the highest concentration of rice in ORS (80 g/l) is drinkable by patients, and is highly effective; at this concentration rice-ORS provides four times more calories than does standard glucose- ORS. 754 RICE-BASED ORAL REHYDRATION SOLUTION 755 Since rice is so effective, what about other cereals? Different countries use different sources of starch, such as maize, wheat, sorghum and potato. The cost, availability, acceptability, feasibility of preparation, chemical quality, and digestibility of each of these should be investigated, as well as their clinical efficacy in an ORS. The reactions of patients during diarrhoeal episodes and following recovery must be observed, and must be related to the individual cereal in the ORS. The ultimate objective is to see that ORS is available in every home in the developing countries where diarrhoea is common, and mothers should be able to prepare the solution using the available cereals and familiar recipes. Taking account of local sociocultural practices is as important as having the correct composition of salts and water. Varying the concentration of rice in the ORS yields different results in terms of efficacy and calorie supplemen- tation (8, 10). Other issues such as cost, effective- ness, ease of preparation and administration, and acceptability will also have to be evaluated in future research. ACKNOWLEDGEMENTS This research was sponsored by the International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B), which is supported by countries and agencies that are concerned about the impact of diarrhoeal diseases on the developing world. Current donors assisting the ICDDR,B are AGFUND, Australia, Bangladesh, France, Japan, Saudi Arabia, Sweden, Switzerland, United Kingdom, and USAID. The authors gratefully acknowledge the valuable help of Dr T. Butler, programme head of the Pathogenesis and Therapy Working Group, for smoothly running this research project, at the ICDDR,B's Treatment Centre. The authors are also grateful to the Aga Khan Foundation for its generous support of the rice-ORS studies. RtSUME DIMINUTION DU VOLUME DES SELLES EN CAS DE DIARRHEE AIGUE PAR UNE SOLUTION DE REHYDRATATION ORALE A BASE DE RIZ Trois cent quarante-deux malades souffrant de diarrh6e aqueuse aigue ont e soumis a un essai randomise utilisant une solution de rehydratation orale (SRO) a base de riz ou de glucose. Lors de leur admission, 75%o d'entre eux etaient gravement deshydrates et 70%o positifs pour Vibrio cholerae. Les patients etudies comptaient 185 enfants en- dessous de 10 ans et 157 adultes; 169 ont e traites avec une SRO a base de riz et 173 avec une SRO glucosee. L'age et le poids des malades etaient comparables dans les deux groupes, de meme que la duree et la gravite de la diarrhee. On a d'abord rehydrate par voie intraveineuse ceux qui etaient gravement deshydrates. En cas de deshydratation moderee, le traitement par la SRO a e instaure d'emblee. La quantite moyenne de selles (± ecart = type) recueillie au cours des premieres 24 heures etait plus faible chez les enfants traites par la SRO a base de riz que chez ceux traites par la SRO glucosee (155,2 ± 13 contre 203,8 ± 13,9 ml/kg/ 24 h; P< 0,01). On a retrouve le merne phenomene chez les adultes avec des valeurs correspondantes de 115 ± 10,1 contre 158,7 ± 12,8 ml/kg/24 h (P< 0,05). Chez les enfants, la prise moyenne de SRO a base de riz et de SRO glucosee (± ecart = type) etait respectivement de 263,5 ± 12,3 contre 379,6± 17 ml/kg/24 h (P<0,05); chez les adultes, les chiffres correspondants etaient de 180,5±7,6 et de 247 ± 14,2 ml/kg/24 h. Dans tous les groupes on a observe un gain d'environ 10% par rapport au poids lors de I'admission dans 1'essai. Les six cas (4 enfants et 2 adultes) insensibles a la rehydratation orale apres therapie intraveineuse, appartenaient tous au groupe de la SRO glucosee. REFERENCES 1. HIRSCHHORN, N. & DENNY, K. M. Oral glucose electrolyte therapy for diarrhea: a means to maintain or improve nutrition? American journal of clinical nutrition, 28: 189-192 (1975). 2. INTERNATIONAL STUDY GROUP. A positive effect on the nutrition of Philippine children of an oral glucose electrolyte solution given at home for the treatment of diarrhoea. Bulletin of the World Health Organization, 55: 87-94 (1977). 756 A.M. MOLLA ET AL. 3. PALMER, D. L. ET AL. Comparison of sucrose and glucose in the oral electrolyte therapy of cholera and other severe diarrheas. New England journal of medicine, 297: 1107-1110 (1977). 4. CHATTERJEE, A. ET AL. Evaluation of a sucrose/electrolyte solution for oral rehydration in acute infantile diarrhoea. Lancet, 1: 1333-1335 (1977). 5. SANDHU, B. K. ET AL. Oral rehydration in acute infantile diarrhoea with a glucose polymer electrolyte solution. Archives ofdisease in childhood, 57: 152-154 (1982). 6. NALIN, D. R. ET AL. Effect of glycine and glucose on sodium and water absorption in patients with cholera. Gut, 11: 768-772 (1970). 7. FIELD, M. New strategies for treating watery diarrhea. New England journal of medicine, 297: 1121-1122 (1977). 8. MOLLA, A. M. ET AL. Rice-powder electrolyte solution as oral therapy in diarrhoea due to Vibrio cholerae and Escherichia coli. Lancet, 1: 1317-1319 (1982). 9. SCHULTZ, S. G. Sodium-coupled solute transport of small intestine: a status report. American journal of physiology, 233: E249-254 (1977). 10. PATRA, F. C. ET AL. Is oral electrolyte solution superior to glucose electrolyte solution in infantile diarrhoea? Archives of disease in childhood, 57: 910-912 (1982). 11. MEEUWISSE, G. W. High sugar worse than high sodium in oral rehydration solutions. Acta paediatrica Scandinavica, 72: 161-166 (1983). 12. HIRSCHHORN, N. ET AL. Decrease in net stool output in cholera during intestinal perfusion with glucose- containing solutions. New England journal of medicine, 279: 176-181 (1968). 13. BOOTH, 1. W. & HARRIES, J. T. Oral rehydration therapy: an issue of growing controversy. Journal of tropical pediatrics, 28: 116-123 (1982). 14. WORLD HEALTH ORGANIZATION. Treatment and prevention of acute diarrhoea. Guidelines for the trainers of health workers. Geneva, 1985, p. 13.