Introduction of Hypo-osmolar ORS for Routine Use

Study site: The Dhaka and the Matlab Hospitals of ICDDR, B: Centre for Health and Population Research.

Duration: Total duration of 15 months that include data collection over a full year to capture seasonal variations in the aetiology of diarrhoea.

Sample size: Based on the yearly patient visits it is estimated that 60,000 patients would be studied at the Dhaka Hospital and 15,000 patients at the Matlab Hospital.

Inclusion criteria

All patients attending the Dhaka and Matlab hospitals who will be admitted to the Short Stay Ward with uncomplicated watery diarrhoea would be eligible for this study.

Exclusion criteria

Patients with complications, and those with severe illness that require special care or multiple interventions would be excluded.

Procedures

Infants 6 month of age or younger would receive the glucose-based (75 mmol/L) ORS ( Na: 75, Cl: 65, K: 20, citrate:10, glucose: 75, and osmolarity: 245 mOsm/L), and those older than 6 months would receive the rice-based ORS (40 g/L of rice powder); both will contain 75 mmol/L of sodium, 65 mmol/L of chloride, 20 mmol/L of potassium, and 10 mmol/L of citrate with an in vitro osmolarity of 170 mOsm/L. This is in line with the Centre's policy of not adding starch for management of infants 6 months of age or younger.

Surveillance and case management

Dhaka Hospital: From our experience about 3% patients (1,800 patients/year) initially admitted to the Short Stay Ward are subsequently admitted to the Longer Stay Wards due to development of symptoms like seizure, lethargy or altered consciousness. Patients admitted to the Short Stay Ward who receive ORS solution for 8 hours or more, and subsequently admitted to inpatient ward for the above symptoms will be evaluated to determine if they are due to hyponatraemia. Similarly, 3% of the patients attending the Matlab Hospital (340 patients/year) might develop these symptoms and will be evaluated if their symptoms are due to hyponatraemia.

All clinical and laboratory data of these patients will be maintained during the study.

Assessment and management of patients Hospitals current protocol for assessment of the cause of lethargy and seizures such as estimation of plasma glucose, serum electrolytes, fever, and study of the cerebrospinal fluids where clinically indicated would be employed for diagnosing the aetiology of the symptoms.

Protocol for management of seizure

Although rare, the development of seizures during the rehydration therapy for acute watery diarrhoea would be considered as a serious adverse event. Patients developing such symptoms would be assed to determine if they could be attributed to hyponatraemia. The same protocol for management of seizure would be used at both of the study sites, which would be as follows:

Procedures:

- All patients developing significant lethargy and seizure while on ORS would be immediately admitted to the special care unit.

- An intravenous line will be opened for medication.

- Blood glucose will be measured immediately from finger blood sample using bedside glucose monitoring machine, and blood sample would be obtained for estimation of serum electrolytes, calcium, and magnesium at the clinical laboratories of the Centre.

- Hypoglycaemic (<2.2 mmol/L) patients would be immediately given intravenous glucose (25% glucose; 2 ml/kg), which would be followed by oral (or through nasogastric tube of patients who are unable to drink) administration of 10% glucose in a dose of xxxxx

- Diazepam (0.3 mg/Kg) would be administered to patients who are not hypoglycaemia, and also to patients who are hypoglycaemic but do not respond to initial glucose infusion.

- If seizure persists, the same dose of intravenous diazepam would be repeated for the second time, and injectable phenobarbitone would also be administered (15-20 mg/kg loading dose, followed by 2.5 mg/Kg every 12 hours as the maintenance dose).

- After control of seizure, a lumber tap will be done to rule out meningitis if clinically indicated (i.e. patients suspected to have meningitis).

- A sample of blood will also be sent for culture to exclude septicaemia

- X-Ray chest will be done to exclude pneumonia if clinically indicated (following WHO guidelines)

- Patients with a serum sodium of ≤120 mmol/L will be treated with 3% NaCl in a dose of 1 ml/Kg.hour for the next 4 hours (i.e. total of 12 ml/Kg over the 4-hour period), along with restriction of plain water.

- Hypernatraemic patients (serum sodium >150 mmol/L) would be treated with the same ORS but with provision for water ad lib.

- Patients suspected for extra intestinal infection including sepsis will be treated with Inj. Ampicillin and Inj. Gentamicin (infants aged 3 months or younger) or Inj. Ceftriaxone and Gentamicin (patients aged more than 3 months) for 7 days.