Rice-flour-based oral rehydration solution for diarrhoeal diseases

Dehydration and electrolyte imbalance, the main causes of morbidity and mortality in diarrheal diseases, have been treated with glucose-based oral rehydration solutions. However, there have been difficulties due to unavailability, cost and unpalatable solutions. 300 children, from age 4 weeks to 12 years, in Jaffna, Sri Lanka, were treated with rice-flour based oral rehydration solution (ORS). This solution was made by boiling 50g. rice flour with 1 liter water and adding a prepackaged salt packet. 50 grams of rice flour is hydrolyzed to produce 35 grams glucose, 4.35 grams protein and 165 kilocalories. 3 children required hospitalization for intravenous therapy, but the rest responded well to the rice flour based ORS. Diarrhea resolved within 2 to 4 days. The rice flour and salt packet together cost Sri Lanka Rs 1.50 (US$0.06), which is significantly less than the glucose based ORS, which costs Sri Lanks Rs 5.00 (US$0.20). Rice-flour based ORS was found to be an inexpensive, palatable, easily available, and an effective alternative to glucose-based formulas.     

Treatment of severe diarrhoeal dehydration in hospital and home by oral fluids

This paper reports on 1330 infants, from birth to 24 months old, suffering from diarrhoea and moderate to severe dehydration who were hospitalized in Tehran University Hospital over a period of 11 months. Fifteen per cent of them had signs of shock and 36% had marasmus. All patients were treated orally in two phases: rehydration therapy and maintenance therapy. For rehydration, an isotonic fluid (sodium 80 mmol l-1, potassium 20 mmol l-1) was administered at a rate of 40 ml kg-1 h-1 until all signs of dehydration disappeared. Following complete hydration, the patients were discharged and maintenance therapy was performed at home, by mothers, administering Maintenance Solution (sodium 40 mmol l-1, potassium 30 mmol l-1) ad libitum. Intravenous fluids were not used, even in severe dehydration. The efficacy and safety of this regimen were confirmed by rapid and successful rehydration in 99.7% of the patients and correction of a wide variety of electrolyte abnormalities present on admission, though some relapsed. The study suggests that this protocol could be employed in varied types and severities of dehydration and electrolyte abnormalities, and could also be used in both well nourished infants and in those with severe marasmus. It also demonstrates that mothers can serve as effective health workers and can perform successful maintenance therapy. Nine per cent of treated children required readmission to hospital within 24 h of discharge and a further 8% were hospitalized elsewhere with recurrent symptoms.     

Can village mothers prepare oral rehydration solution?

Both the prepackaged glucose-electrolyte powder and the domestic rehydration solution have received wide publicity, yet there has been little evaluation of how accurate the mother can be in preparing the mixture. The 2 studies described here attempted to measure this human factor in actual field situations in India and Trinidad. The 1st study attempted to quantify the variability in the size of the 2-finger and thumb pinch of salt. The 2nd study measured the different concentrations when mothers diluted a standard packet of glucose and electrolytes in domestic vessels. In India and Trinidad, mothers of children with diarrhea were instructed about making up local salt-sugar-water mixtures for home treatment. They were shown how to take a 2-finger and thumb pinch of salt in a way which had previously been agreed upon. Multiple pinches--5 in Trinidad and 10 in India--were then weighed on standard laboratory scales to find the average salt picked up. The fingers of the mothers were measured to see if the weight of salt picked up correlated with hand size. Other factors which could influence the pinch size were also considered: type and quality of salt available and the relative humidity. In the packet dilution study, mothers in rural India were instructed in the local language by an indigenous nurse who used diagrams in the teaching. The glucose concentrations of the mixture made up by 66 village mothers were analyzed in the field by a pocket refractometer. The finger-pinch method of measuring salt was very inaccurate in field tests. At least 1 mother in 20 would pick up double the amount of salt intended. There was no statistical correlation between finger size and the weight of a pinch of salt. In the packet dilution study there was a wide range of concentrations, but over 83% of the mothers mixed the solution to within 40 mmol/liter of the "correct" value.     

Assessment of the effectiveness of oral rehydration therapy against severe diarrheal dehydration.

A hospital based case-control study for assessing the effectiveness of oral rehydration therapy (ORT) preparation against severe dehydration due to diarrhea was conducted at the Infectious Diseases Hospital, Jakarta, Indonesia. A total of 202 children aged 24 months or less who attending the hospital were suffering from acute watery diarrhea were recruited in the study. Those who were severely dehydrated as assessed by WHO criteria were accounted as cases; those who were non-severely dehydrated were accounted as controls. There were 59 cases and 143 controls. A questionnaire was used to interview all study subjects' mothers about ORT usage and various risk factors. Mothers who used ORT were asked to show how they prepared either oral rehydration solution (ORS) or sugar salt solution (SSS). Effectiveness of ORT against severe diarrheal dehydration was based on the formula for assessment of vaccine efficacy by using the odds ratio (OR). With the use of the logistic regression method, an adjusted OR was obtained after controlling various confounders. The effectiveness of ORT against severe diarrheal dehydration was 72.1% for proper ORT preparation and was decreased to 63.2% when ORT was improperly prepared.     

Evaluation of home-made salt-sugar oral rehydration solution in a rural Nigerian population

Standardized local measures for preparing oral rehydration solution (ORS) in Nigeria were re-evaluated under laboratory conditions. Our results confirm those of the standardization team in respect of granulated and cube sugar. However, our mean weight of one salt measure (2.8155 +/- 0.292 g) is about 20% greater than their value. Consequently, correct use of the measures in our study gave solutions of 211-297 mmol-1 total concentration and 60-80 mmol-1, Na+ as against their values of 173-251 mmol 1-1 and 45-70 mmol-1, respectively. This discrepancy is most likely due to differences in salt type. Analysis of home-made solutions prepared by 40 illiterate mothers showed that 60% of them made accurately composed solutions. All the rest made hypertonic solutions. Salt type, spoon size and levelling technique are all possible causes of their error. The tendency to err only on the side of greater rather than lower salt concentration may be culture based or simply due to natural maternal instinct. To combat this trend, health education programmes in Nigeria should emphasize the danger in feeding a hypernatremic solution to a dehydrated child.     

How much oral rehydration solution is actually administered during home-based therapy?

In some parts of the world up to one-half of all deaths in young children are attributable to dehydration associated with diarrhoea. As a countermeasure, mothers in underdeveloped countries are being successfully taught to give oral rehydration solution at home. There are, however, serious doubts as to whether mothers give their children enough. The focus of our investigation was a methodology capable of establishing the exact quantity of fluid administered by unsupervised mothers at home. Accurate quantitative data are essential for programme planning and evaluation. In our sample of 44 cases, only two children received more than 90 ml kg-1 day-1. The mean observed value was 44 ml kg-1 day-1 (SD 28.4); well below the recommended dosage. Preliminary data were also gathered on natural consequences which may discourage use of ORS such as vomiting, increased frequency of watery stools, and distaste for the solution.     

Severe oral symptoms after the use of an oral solution containing ketoprofen in two NSAIDs-sensitive patients.

Cutaneous application of the nonsteroidal anti-inflammatory drug (NSAID) ketoprofen has been reported to induce contact dermatitis. However, there is no report of intraoral symptoms after the use of solutions containing this drug. In this report we describe two cases of severe intraoral symptoms after the use of a gargle containing ketoprofen in two patients with NSAIDs hypersensitivity. The patients underwent diagnostic procedures 6 months after the episodes of intraoral symptoms. Procedures included skin prick test for inhalant and food allergens, and total- and specific-IgE determinations to evaluate the presence of atopy. A single-blind, placebo-controlled challenge with different dilutions (1/1000, 1/100, 1/10, and 1/1) of ketoprofen oral solution was carried out by a modified version of a standardized protocol. We used the same commercial solution without the drug as placebo. Diagnostic procedures failed to demonstrate allergic sensitization to the common inhalant and food allergens. Both patients experienced a slight intraoral itching and edema of the lips a few minutes after the intraoral use of 1/100 dilution of active drug. Our cases suggest that the contact of an oral solution containing ketoprofen with oral mucosa may induce locally severe oral manifestations. Patients with NSAIDs sensitivity should be warned on the potential risk of using an oral solution containing this class of drugs.     

Absorption of a hypotonic oral rehydration solution in a human model of cholera.

The development of oral rehydration solutions (ORSs) has been one of the important therapeutic advances of this century. The optimal formulation, however, of ORSs for both cholera and other infective diarrhoeas is still debated. Part of the problem in developing ORSs has been the lack of adequate test systems for the assessment of new formulations before clinical trial. We have developed a jejunal perfusion, cholera toxin induced, secretory model in humans and have compared net water and solute absorption from a hypotonic ORS (HYPO-ORS: sodium 60 mmol/l, glucose 90 mmol/l, osmolality 240 mOsm/kg) and the British Pharmacopoeia recommended ORS (UK-ORS: sodium 35 mmol/l, glucose 200 mmol/l, osmolality 310 mOsm/kg) in six healthy volunteers. A plasma electrolyte solution (PES) was also perfused in all subjects to confirm a secretory state. Only HYPO-ORS reversed sodium secretion to absorption (p < 0.01). Both ORSs promoted net water absorption but this was greatest with HYPO-ORS (p < 0.01). Glucose and potassium absorption rates were similar for both ORSs whereas chloride absorption mirrored sodium absorption and was greatest from HYPO-ORS (p < 0.05). These results, in a biologically relevant model of secretory diarrhoea, suggest it may be possible to achieve improved rates of rehydration by the use of hypotonic ORS with mid range sodium concentrations.     

The effects of rehydration on cycling performance after exercise-induced dehydration

The effects of 7.6% carbohydrate-electrolyte solution (CES) and placebos (P) on rehydration (R) after exercise-induced dehydration and on a subsequent time-trial (TT) of cycling performance were studied. Thirteen male subjects exercised in a thermally-controlled environment (28 degrees C, 63% RH) until 3% of their body weight was lost. After exercise, the subjects moved to a neutral environment (22 degrees C) and rested for 30 minutes prior to a 2-hour R period. During R, subjects were fed CES or P to a maximum volume of 120% of previous body mass loss at 0, 30, and 60 minutes, in bolus-doses of 50%, 40% and 30% respectively. After R, subjects performed a 1-hour TT with no further fluid intake. % R with CES was significantly higher than with P (70 +/- 3% vs 60 +/- 5%; p < 0.01). During the TT, blood glucose dropped in the CES group but not in the P group. It was found that, despite a more effective R with CES, the performance results did not differ between groups (65.1 +/- 2.2 minutes and 65.2 +/- 2.3 minutes for CES and P respectively). It is suggested that an insulin-mediated rebound effect on CHO metabolism during TT, in which no further CHO was supplied, nullified the benefits of rehydration.     

Antidiarrheal effects of L-histidine-supplemented rice-based oral rehydration solution in the treatment of male adults with severe cholera in Bangladesh: a double-blind, randomized trial

BACKGROUND: Because of the antisecretory potential of L-histidine in the intestinal tract, its antidiarrheal effects were determined in cholera. METHODS: In a double-blind trial of 126 adult male patients with cholera, L-histidine (2.5 g/L) was mixed with a rice-based oral rehydration solution (ORS) and administered to 62 patients; 64 patients received the same ORS without L-histidine. All patients received ciprofloxacin at a dosage of 500 mg every 12 h for 72 h. Fluid output (of stool, urine, and vomit) and intake (of ORS, water, and intravenous fluid) were determined every 8 h for 72 h. RESULTS: Administration of ORS with L-histidine significantly (P<.05) reduced the frequency of stool output during 32-64 h after initiation of ORS treatment, compared with that in patients given ORS without L-histidine ([all data are means+/-SD] 32-48 h, 11.5+/-6.9 mL/kg vs. 18.8+/-16.0 mL/kg; 40-48 h, 6.7+/-4.4 mL/kg vs. 11.5+/-9.7 mL/kg; and 56-64 h, 6.3+/-5.8 mL/kg vs. 7.8+/-4.1 mL/kg). An overall reduction of 22% in the volume of stool was observed in patients given ORS without L-histidine. The amount of required unscheduled intravenous fluid was lower in patients given ORS with L-histidine, compared with that in patients given ORS without L-histidine (0-24 h, 82.5+/-44.4 mL/kg vs. 158.6+/-72.2 mL/kg [P<.01]; and 24-48 h, 41.6+/-40.4 mL/kg vs. 52.5+/-22.1 mL/kg [P>.05]). Administration of ORS with L-histidine also significantly reduced (P<.05) the intake of ORS and the duration of illness. No adverse effects were observed in these patients. CONCLUSIONS: L-histidine reduces the weight of stool and the frequency of stool output in cholera and could be a useful and safe adjunct treatment that will increase the success rate of ORS and antibiotic therapy in cholera.     

First do no harm: making oral rehydration solution safer in a cholera epidemic.

Oral rehydration solution (ORS) is lifesaving therapy for cholera and pediatric diarrhea. During a cholera epidemic in Guinea-Bissau, we evaluated the microbiologic quality of ORS prepared at a hospital and tested a simple intervention using special vessels for disinfecting tap water with bleach and for preparing, storing, and dispensing ORS. Few coliform bacteria and Escherichia coli were recovered from tap water; however, pre-intervention ORS contained numerous bacteria including E. coli and toxigenic Vibrio cholerae O1. In contrast, ORS samples from intervention vessels had few or no coliform bacteria, no E. coli, and no V. cholerae. Mean pre-intervention counts of coliform bacteria (3.4 x 10(7) colony-forming units [cfu]/100 ml) and E. coli (6.2 x 10(3) cfu) decreased significantly during the intervention period to 3.6 x 10(2) cfu and 0 cfu, respectively (P < 0.001). This simple system using bleach disinfectant and special storage vessels prevents bacterial contamination of ORS and reduces the risk of nosocomial transmission of cholera and other enteric pathogens.     

Search for the ideal oral rehydration solution: studies in a model of secretory diarrhoea.

In situ perfusion of whole rat small intestine was used to compare the efficacy of five oral rehydration solutions in promoting water and sodium absorption in normal intestine and secreting intestine after exposure to cholera toxin. Solutions varied in their sodium (35-90 mmol/l) and glucose (111-200 mmol/l) concentrations, molar ratio of glucose:sodium (1.2-5.8), and osmolality (281-331 mOsmol/kg), and contained either bicarbonate (18-30 mmol/l) or citrate (10 mmol/l). In normal intestine all solutions promoted net water absorption. Cholera toxin induced reproducible water secretion but all solutions reversed this to absorption. Water absorption was greatest with solutions containing sodium 60 mmol/l and glucose 111 or 140 mmol/l, and with a glucose:sodium ratio approximately 2, in both normal and secreting intestine. All solutions promoted net glucose absorption in both normal and secreting intestine. Net sodium absorption occurred with solutions containing greater than or equal to 60 mmol/l sodium in normal intestine but sodium secretion occurred from all solutions in secreting intestine. Sodium movement was directly related to the sodium concentration of the solution and sodium secretion occurred despite net water and glucose absorption. We consider that these studies may guide future development of oral rehydration solutions.     

Furazolidone for treatment of diarrhoeal disease

Furazolidone, a synthietic nitrofuran, is active against a broad spectrum of bacteria and Giardia lamblia. Since 1954, furazolidone has been used almost exclusively for the specific and symptomatic treatment of infectious diarrheal diseases. Diarrheal disease is the leading cause of death of children and a major contributing factor of malnutrition in the developing world. It can be avoided with proper water and waste treatment, personal hygiene, and food preparation. The most critical aspect of treating acute diarrhea is maintaining optimal hydration and electrolyte balance. Fluid and electrolyte replenishment must constitute the 1st line of therapy. Antimicrobial therapy, however, improves the outlook further. Effective antimicrobials reduce the average duration of illness and the likelihood of relapses, complications and death. The ideal antimicrobial for treating acute diarrhea is a single broad-spectrum antimicrobial agent of low toxicity that would be effective for empirical treatment of acute diarrheal disease. During 30 years of clinical use worldwide, the effectiveness of furazolidone has shown to be comparable or superior to that of other drugs used to treat these diseases. Because furazolidone has fairly low toxicity, it is a relatively safe drug. The most common reaction appears to be gastrointestinal distress, though dizziness, drowsiness, headaches, and general malaise have also been reported. A drug that acts specifically on its target is generally preferable to one with less specific activity. Furazolidone inhibits a variety of bacterial enzymes, an activity that minimizes the development of resistant organisms. Furazolidone is a single, broad-spectrum antimicrobial that is effective, relatively safe, specific, and is orally administered in tablet or suspension form.     

Rehydration and maintenance therapy of cholera patients in Jakarta: citrate-based versus bicarbonate-based oral rehydration salt solution

We compared the therapeutic efficacy of a World Health Organization standard bicarbonate-based oral rehydration salt solution (BBORS) with a citrate-based oral rehydration solution (CBORS) in a randomized, double-blind, controlled trial in 130 dehydrated patients with cholera aged three to 82 years. On admission the 70 patients who received CBORS and the 60 who received BBORS were similar except that the serum CO2 content (mmol/liter) was significantly lower in the CBORS group (10.8 +/- 3.6 vs. 12.5 +/- 5.3). The incidence of vomiting postadmission (41% vs. 62%, respectively), the stool output during the first 24 hr (4,252 +/- 3,900 ml vs. 6,025 +/- 4,389 ml, respectively), and the time until the patients' conditions were considered normal (38.9 +/- 14.5 hr vs. 46.3 +/- 22.7 hr, respectively) were all significantly less in the CBORS group. The serum CO2 content increased more rapidly during the first 48 hr in the CBORS group (87% +/- 74% vs. 61% +/- 68% for the BBORS group); 23% of the patients receiving CBORS and 35% of the patients receiving BBORS were considered oral-therapy treatment failures. The results indicate that CBORS was superior to BBORS for rehydration and maintenance therapy of hospitalized cholera patients in Jakarta.     

Effective oral treatment of unconjugated hyperbilirubinemia in Gunn rats

We sought to develop an oral treatment for unconjugated hyperbilirubinemia. In the Gunn rat model of unconjugated hyperbilirubinemia, dietary supplementation with the lipase inhibitor orlistat (Orl) or with calcium phosphate (CaP) decreases plasma unconjugated bilirubin (UCB) levels. We determined whether Orl, CaP, or their combination is superior to phototherapy, the conventional treatment, and whether the effects of Orl and CaP are influenced by dietary fat content. Gunn rats were treated with Orl (200 mg/kg chow), CaP (20 g/kg chow), Orl + CaP, or continuous phototherapy (19 muW/cm(2)/nm) during a low-fat (LF) diet (13 energy%) or high-fat (HF) diet (35 energy%). Plasma UCB and fecal fat excretion were measured before, during, and/or at the end of treatment. Orl treatment for 2 weeks (HF diet) reduced plasma UCB concentrations similar to phototherapy (-34% and -28%, respectively); the combination of both was more effective than either treatment alone (-48%; P < .001). After 3 weeks of a HF diet, plasma UCB was 46% lower compared with the LF diet (P < .001). Plasma UCB concentrations were negatively correlated with fecal fat excretion (r = -0.96; P < .001). Irrespective of dietary fat content, 3 weeks of combined treatment (Orl + CaP) decreased plasma UCB by approximately 50% (P < .01) and was more effective than phototherapy (P < .05) at the intensity provided. In conclusion, plasma UCB concentrations in Gunn rats are negatively related to fecal fat excretion and dietary fat content. Orlistat is equally effective as phototherapy for the treatment of unconjugated hyperbilirubinemia in Gunn rats, and combined oral treatment with Orl + CaP is more effective than phototherapy. The present results support the feasibility of an efficient oral treatment of unconjugated hyperbilirubinemia.