Effective treatment of diarrhoeal dehydration with an oral rehydration solution containing citrate

To compare the clinical efficacy of oral rehydration salts (ORS) from effervescent tablets containing citrate with the WHO recommended ORS for the treatment of dehydration due to acute diarrhoea, a randomized clinical trial was carried out in 57 adults and 58 children. These patients had mild or moderate degrees of dehydration and acidosis due to acute watery diarrhoea that was caused by enterotoxigenic Escherichia coli in 43-47% of the cases. Efficacies were compared by measuring oral fluid intake, stool output, gain in body weight, decrease in serum specific gravity and correction of acidosis during treatment. Successful rehydration and maintenance of hydration was achieved in 25 adults and 24 children treated with citrate containing ORS and 25 adults and 24 children treated with WHO ORS. The mean intake of ORS/kg body weight in children receiving WHO ORS was greater (p less than 0.05) and correction of acidosis was faster than the citrate group during the initial 24 h of therapy (p less than 0.05). By 48 h, however, both groups showed satisfactory and comparable intake of ORS and correction of acidosis. Thus ORS from effervescent tablets containing sodium citrate base is effective for management of diarrhoea in both adults and children and is a convenient stable form of ORS for use in the home and for travelers.     

Training rural health staff for oral rehydration therapy in southern Sudan

From February 1980 to August 1982 a very definite change occurred in the treatment pattern for diarrhoea among the rural health staff in Torit and Kapoeta districts in Eastern Equatoria Province in Sudan. This paper describes a training and supervision programme for promoting use of ORT in diarrhoeal diseases and at the same time discouraging the use of sulphonamides in simple diarrhoea. In the training programme emphasis is put on increasing the knowledge of the health staff both about the medical facts and about communication with their communities. ORS as treatment for diarrhoea has been well accepted by the public, who consider the sugar/salt solution as "good medicine". The use of sulphonamides for diarrhoea has decreased from 75% to 22% of the diarrhoea cases, while use of ORS has increased from 7% to 72% of the diarrhoea cases.     

Airlangga scoring system for prediction of dehydration in diarrheal patients

To investigate the predictive factors for dehydration in acute diarrheal patients, this case control study was conducted using the observational analytic method. Acute diarrheal patients who were admitted to the Hospital and Outpatient Pediatric Clinic, Dr Soetomo Hospital, were included in this study. By discriminant analysis, three significant variables were determined to differentiate dehydration risk in acute diarrheal patients: frequency of stool, amount of feces in the stool, and severity of vomiting (power test: 70.0%). Significant differences were found between the groups with and without dehydration for stool frequency each day (p<0.05), amount of stool per day (p<0.05), and severity of vomiting (p<0.05). Frequency of stool, amount of stool, and severity of vomiting are predictive factors for dehydration in acute diarrhea.     

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.     

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.     

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.     

Sodium content of oral rehydration solutions: a reappraisal.

Proper choice of oral rehydration solution, with regard to sodium content, is a conflicting issue to general practitioners and pediatricians. World Health Organization (WHO) recommendations of oral rehydration solution containing 90mmol/1 sodium, have been effective throughout developing countries worldwide. In developed countries, however, such as England, this recommendation seems inappropriate; a recommendation of 50 - 60 mmol/1 sodium with 90 -111mmol/1 glucose is preferred. This combination will eliminate the need for free water recommended by the WHO maintenance therapy. Normonatraemia is maintained, and hyponatraemia and hypernatraemia can both be corrected. Sodium content is adequate in replacing stool loss resulting from viral and bacterial diarrheas. Iatrogenic hyponatraemia and hypernatraemia do not occur as they would with oral rehydration solutions with low (30-35) or high (90mmol/1) sodium concentration. Solutions containing 50-60 mmol/1 sodium is safer in neonates and young infants with immature renal functions, incapable of properly distributing increased sodium leads. Glucose concentration necessary to make oral rehydration with 50 - 60 mmol/1 isotonic, or hypotonic, resembles WHO - ORS, but is half that in 30-35 mmol/1 sodium solutions. In controlled clinical trials, oral rehydration solutions with 50-60 mmol/1 sodium have proven safe, and performance was compatible with WHO-ORS. For both rehydration and correction of acidosis, the solution proved effective. When oral rehydration solution sodium, concentrate is below 90 mmol/1, errors in reconstituting may be common, but offers less risk resulting in dangerous hypernatraemia. An "all purpose" physiological oral rehydration solution would make oral rehydration therapy, more economical, simpler, and safe in developed countries worldwide.     

Patterns of use of oral rehydration therapy in Srinagar (Garhwal), Uttaranchal,India

A study was conducted to assess the knowledge of preparing packet oral rehydration solution (ORS) and home-made salt-sugar solution (SSS) among mothers in Srinagar (Garhwal), Uttaranchal. Two hundred and twenty-five mothers were interviewed. Only a small proportion recognized the ORS packets (18.66%) and only 17.77% mentioned the correct method of preparing a solution from a packet (even after reading the instructions on the packet). Homemade SSS was adequately discussed by only 6.22% mothers and they were taught to correctly prepare and administer ORS and home-made SSS. After the educational programme, significant (P < 0.001) improvement in their knowledge was found. Eighty-six per cent knew the correct method of preparing packet ORS and 80.88% the correct method of preparing homemade SSS (P < 0.001). Interventions of this kind should be carried out to improve the knowledge and skills of mothers in treating childhood diarrhoea.     

Effect of bicarbonate on efficacy of oral rehydration therapy: studies in an experimental model of secretory diarrhoea.

In situ perfusion of rat intestine was used to evaluate the effect of bicarbonate on the efficacy of a low sodium (35 mmol/l) glucose-electrolyte oral rehydration solution in normal and cholera toxin-treated rat small intestine. In normal intestine, absorption of water was greater (108 (8.1) microliters/min/g; p less than 0.01) and sodium secretion less (-4.3 (0.3) mumol/min/g; p less than 0.01) from the oral rehydration solution containing bicarbonate than from the solution in which bicarbonate was replaced by chloride ions (59.5 (7.2) microliters/min/g and -7.8 (0.8) mumol/min/g, respectively). Glucose absorption in normal intestine was similar with both solutions. In the secreting intestine, both oral rehydration solutions reversed net water secretion to absorption, but inclusion of bicarbonate resulted in significantly less net absorption of both water (2.18 (6.9) microliters/min/g; p less than 0.05) and glucose (18.7 (2.1) mumol/min/g; p less than 0.001) compared with bicarbonate free oral rehydration solution (19.4 (3.9) microliters/min/g and 35.8 (3.7) mumol/min/g, respectively). Net sodium secretion occurred in normal and secreting intestine but was significantly less with the bicarbonate containing oral rehydration solution. These findings suggest that the demonstrable advantage of bicarbonate in promoting water absorption from this oral rehydration solution in normal rat intestine does not apply to cholera toxin treated secreting intestine.     

Safety and effectiveness of long-term therapy with the oral iron chelator deferiprone

The identification of a safe, orally active iron chelator is critically important for the prevention of morbidity and early death in patients receiving regular red cell transfusions. Based on our findings in a 1-year multicenter, prospective study of the safety and efficacy of deferiprone in patients with thalassemia major, we have extended the treatment period to 4 years. The mean dose of the chelator was 73 mg/kg per day during 531 patient-years. The rates of agranulocytosis (absolute neutrophil count [ANC] < 500 x 10(9)/L) and milder forms of neutropenia (ANC, 500-1500 x 10(9)/L) were 0.2 and 2.8 per 100 patient-years, respectively. Neutropenia occurred significantly more commonly in patients with intact spleens. Gastrointestinal and joint symptoms decreased significantly after the first year of therapy, and led to discontinuation of deferiprone in only one patient in years 2 to 4. The mean alanine aminotransferase (ALT) value of 71 U/L after 4 years of therapy was significantly higher than the baseline value of 61 U/L. Trend analysis showed no increase in the ALT levels or the percentage of patients with ALT levels greater than twice the upper limit of the reference range. Ferritin levels did not change significantly from the values at the time of change from deferoxamine to deferiprone in either the intention-to-treat analysis or in the 84 patients who completed 4 years of therapy. Because of concerns regarding the effectiveness of the studied dose of deferiprone, 47 patients discontinued therapy, whereas 15 patients interrupted therapy because of concerns regarding low iron levels. The results of this study help to define the safety and effectiveness of long-term therapy with deferiprone.     

Evaluation of the efficacy of oral rehydration solutions using human whole gut perfusion.

Whole gut perfusion in humans was used to compare the effect on intestinal water and electrolyte transport of the World Health Organisation oral rehydration solution (solution II, composition in mmol/l: glucose 111, sodium 90, bicarbonate 30, potassium 20; 308 mOsm/kg); a hypertonic commercial oral rehydration solution (solution III, glucose 188, sodium 50, bicarbonate 20, potassium 20 mmol/l; 335 mOsm/kg); and three experimental bicarbonate free, hypotonic oral rehydration solutions: solution IV (glucose 111, sodium 60, potassium 20 mmol/l; 260 mOsm/kg), solution V (glucose 80, sodium 60, potassium 20 mmol/l; 219 mOsm/kg), and solution VI (glucose 80, sodium 30, potassium 20 mmol/l; 177 mOsm/kg). Perfusion of the intestine with a standard cleansing solution (solution I, sodium 125, potassium 10, bicarbonate 20, sulphate 40, mannitol 80 mmol/l; 275 mOsm/kg) confirmed published data on minimal water and sodium absorption. Experimental solution VI produced maximum water absorption (mean (SE) +1660.0 (29.8) ml/h) significantly greater than solution II (+1195.3 (79.5) ml/h), III (+534.7 (140.3) ml/h), IV (+1498.0 (42.7) ml/h), and V (+1327.7 (24.4) ml/h; p less than 0.05). Sodium absorption was significantly greater with solution II (+97.4 (7.9) mmol/h) compared to VI (+43.3 (7.8) mmol/h; p less than 0.01) but not compared to IV (+67.2 (13.0) mmol/h). A hypotonic oral rehydration solution such as solution VI may provide optimal replacement treatment for patients with acute diarrhoea.     

Does oral rehydration therapy alter food consumption and absorption of nutrients in children with cholera?

In order to estimate consumption of food and absorption of nutrients, a metabolic balance study was conducted in 47 children between 1 and 5 years old, suffering from acute cholera. Twenty-two of the children were treated by intravenous solution (IV) only and 25 others by oral rehydration along with intravenous solution (ORS/IV) when necessary. After initial rehydration a nonabsorbable charcoal marker was fed to the patients followed by a typical Bangladeshi home food of known composition offered ad libitum. Appearance of the first marker in the faeces was taken as zero hour (0 h); at 72 h a second marker was fed. Faeces, urine and vomitus were collected up to the appearance of the second marker. Intake of IV fluid, ORS and any other fluid or food were recorded accurately. Samples of faeces, urine and vomitus were analysed for energy, fat and nitrogen. Consumption of nutrients and absorption in both groups were calculated. There was no significant difference in the intake or absorption of energy or carbohydrate between the two groups. The consumption of fat and protein was slightly, but significantly, lower in the ORS/IV group during the acute stage of diarrhoea than in the IV group. Absorption of nitrogen was significantly lower in the ORS/IV group, but absorption of fat was not significantly impaired. Vomiting was significantly higher in the ORS/IV group. The differences in the consumption and absorption of nutrients between the two groups were transient and came to the same level within 2 weeks after recovery.     

Chronic oral sildenafil therapy in severe pulmonary artery hypertension

BACKGROUND: Sildenafil, a selective phosphor-diesterase-5 inhibitor, may be of clincal benefit in patients with pulmonary artery hypertension. METHODS AND RESULTS: Fourteen patients, aged 5-30 years, with severe pulmonary artery hypertension (9 with primary pulmonary hypertension, 5 with operated congenital heart disease) received oral sildenafil in addition to conventional therapy. Twelve patients were in New York Heart Association functional class III or IV. The drug was started in low dose and empirically increased. Finally a median dose of 87.5 mg/day was used in children weighing less than 30 kg, and 150 mg/day in those with weight more than 30 kg. The patients were followed up by assessing their functional status, six-minute walk test, Doppler echocardiography and hemodynamic study (in selected cases). On mean follow-up of 7.3+/-2.4 months (range 3-14 months), New York Heart Association functional class improved from 3.31+/-0.75 to 2.00+/-0.71 (p<0.002). There was a remarkable improvement on the six-minute walk test from a baseline of 264.1+/-193.7 m to 408.2+/-156.97 m at 3 months (p<0.001) and 453.2+/-159.81 (p<0.0001) at 6 months. The right ventricular systolic pressure estimated echocardiographically declined from 112.40+/-45.21 mmHg to 101.86+/-47.86 mmHg (p<0.002). The mean pulmonary artery pressure decreased from 62 mmHg to 47 mmHg in 4 patients of primary pulmonary hypertension recatheterized after a mean of 7 months of sildenafil treatment. Clinical improvement was seen even when no decrease in pulmonary artery pressure was demonstrated in one patient with secondary pulmonary artery hypertension. However, 2 patients died during follow-up despite clinical improvement. CONCLUSIONS: Oral sildenafil was well tolerated and led to an improved clinical condition and exercise performance. Whether the drug improves mortality remains to be established. Larger trials a rewarranted.