Acute Diarrhea and Oral Rehydration Dr. Alaa Jumaa

2 Acute Gastroenteritis Acute Gastroenteritis (AGE) remains a major cause of morbidity and mortality in the USA Over 1.5 million outpatient visits 200,000 hospitalizations 300 death a year Worldwide diarrheal disease is the leading cause of morbidity and mortality million deaths annually among children younger than 5

3 Acute Gastroenteritis Direct medical cost in the US reach $ 250 million/year and is estimated to reach 1 billion worldwide Even though the number of death associated to AGE worldwide is still high, a decrease has been noticed since the start of Oral Rehydration Therapy (ORT) campaigns

4 Choices of ORS In 1975 the WHO and UNICEF decided to promote a single ORS (WHO-ORS) It contained (mEq/L) Na 90, K 20, CL 80, base 30 and Glu 111(mmol/L) with an Osm of 311 This composition allowed for a single solution to be use for treatment of diarrhea caused by a multitude of agents Has been proven to be effective and safe for over 25 year

5 Choices of ORS In 2002 the WHO announced a new ORS formulation with a lower osmolarity 2002 WHO-ORS contains 75mEq/L of Na, 75 mmol/L of Glu and an Osm of 245 Lower osmolarity as been associated to less stool output, less vomiting and reduced need of IV among infants and children with non-cholera diarrhea

6 Choices of ORS SolutionCarbs (gm/L) Sodium (mmol/L Potassium (mmol/L) Chloride (mmol/L Base (mmol/L) Osmolarity (mOsm/L) WHO-ORS (2002) WHO-ORS (1975) Pedialyte Enfalyte Rehydralyte CeraLyte N/A30220 Gatorade Apple Juice N/A730 Coca-Cola1121.6N/A

7 Oral Rehydration Therapy The full benefits of ORT have not been realized in developing countries One of the reasons for the low use of ORT is the ingrained use of IV therapy The vast majority of pediatricians (30-49%) report always using IVF to treat moderate dehydration and 1/3 report using IVF to treat mild dehydration

8 Oral Rehydration Therapy Randomized trials of ORT vs. IV hydration have demonstrated Shorter ED stays Greater parental satisfactions As effective as IV in moderately dehydrated children < 3 years Faster initiation of rehydration Lower hospitalization rate

9 Oral Rehydration Therapy Barriers for ORT Lack of parental knowledge Lack of training of medical professionals Cost of commercially available ORS Preferences among physicians The practice of continued feeding during diarrheal disease have been hard to establish

10 Physiologic Basis of ORT

11 Physiologic Basis of ORT This co-transport remains intact even in infections of E. coli, salmonella, shigella and rotavirus The mechanism essential for the efficacy of oral rehydration solution (ORS) is the couple transport of sodium and glucose in the intestinal brush border

12 Limits of ORT Mild to moderate dehydration from diarrhea of any cause can be treated effectively with ORS except in : 1.patients with severe dehydration 2.those with uncontrollable vomiting 3.those unable to drink because of extreme fatigue 4.stupor, or coma 5.those with gastric or intestinal distention 6.1 % of diarrhea is due to carbohydrate malabsorption

13 Oral Rehydration Therapy ORT includes two phases: Rehydration Phase mild dehydration 50 mL/kg of ORS should be given within 4 hr to patients with mild dehydration and moderate dehydration 100 mL/kg over 4 hr to those with moderate dehydration An additional 10 mL/kg of ORS is given for each stool. feeding should be allowed after rehydration Vomiting may occur during the first 2 hr of administration of ORS, but it usually does not prevent successful oral rehydration

14 Oral Rehydration Therapy Maintenance Phase mild diarrhea Patients with mild diarrhea usually can then be treated at home with 100 mL of ORS/kg/24 hr until the diarrhea stops. severe diarrhea Patients with more severe diarrhea require continued supervision, an intake of 10–15 mL of ORS/kg/hr is appropriate. Breast-feeding or supplemental water intake should be maintained.

15 Flavouring/colouring of ORS The theoretical advantage of flavoured and coloured ORS is greater acceptability, and consequently increased use. Because this, in turn, might lead to over-consumption, the WHO/CDD Programme conducted a safety/efficacy study in Egypt and an acceptability study in the Philippines of flavoured and coloured ORS solutions. The results of these studies showed neither an advantage nor disadvantage for the flavoured and coloured ORS when compared to the standard ORS with regard to safety, acceptability and correct use.

16 Flavouring/colouring of ORS In 1968, cyclamic acid was reported to cause cancer high dose of saccharine are suspected to be carcinogenic; dulcine is recognized as toxic and carcinogenic; and aspartame is known to be unstable at temperatures above 40 degrees Celsius. For all these products, the above mentioned guidelines specify the maximum dose to be consumed per kg of body weight and per day (i.e., aspartame 40 mg/kg body weight/day). it also seems that certain flavouring agents can cause allergies and other side effects, particularly in infants and small children. Finally, it must be noted that the flavouring of ORS may increase cost of the product by up to 20-30%, especially when the additional ingredients must be imported.

17 New advancement The amino acid- and/or maltodextrin-containing ORS Studies to evaluate cooked rice as a replacement for glucose in ORS solution began in Initially, solutions were prepared by cooking rice powder (50-80g/l) for at least 10 minutes and then adding salts in concentrations identical to those of the ORS recommended by WHO. rice-based ORS rice-based ORS is superior to standard ORS for adults and children with cholera, and may be used to treat such patients wherever its preparation is convenient; rice-based ORS is not superior to standard ORS in the treatment of children with acute non-cholera diarrhoea, especially when food is given shortly, after rehydration, as is recommended to prevent malnutrition.

18 The ORS in liquid and tablet form liquid ORS In 1980 TETRA PAK International AB, in collaboration with the Department of Paediatrics of the University of Lund, Sweden, offered to evaluate the production of liquid ORS in aseptic packages and to develop a method to sterilize liquid ORS. The objective was to make liquid ORS available in locations where water supply was problematic, for example after a natural disaster.

19 The ORS in liquid and tablet form ORS in tablet form. With the support of the CDD Programme, the Programme for Appropriate Technology in Health (PATH) developed ORS in tablet form. The manufacturing guidelines became available in Since then PATH has offered a licensing agreement to transfer the technology to manufacturers in developing countries. The formulation of the tablet complies with that recommended by WHO/UNICEF, but contains excipients that are needed to compress the product. It has a size of 15/16 and will make 150 ml of solution. effervescent tablet It disintegrates in less than 90 seconds. Later, CIBA- GEIGY, Basle, Switzerland developed an effervescent tablet for 120 ml of solution, that is now marketed worldwide.

20 Thanks