1. LOW OSMOLARITY ORS: The Advantages (against the motion) Dr Pravakar Mishra,MD Asst. Prof. of Pediatrics SVP PG Institute of Pediatrics, Cuttack 753002 E-Mail:- drpravakar@sify.comdrpravakar@sify.com

2. BACKGROUND Under 5 Diarrhea- 1.5 Billion Episodes & 1.5 to 2.5 Million deaths(5M. 20 yrs. back). JAMA. 2004;291:2628-2631. Widespread use of standard ORS in past 3 decades is with promising results. JAMA. 2004;291:2628-2631. Most diarrhea deaths are caused by dehydration, which can be treated by replacing fluid loss with ORS in over 90% of cases. BMJ 2001;323:59-60

3. ORS development None of the amino acid/ maltodextrin/ rice based ORS have been found superior to standard ORS Bhan MK, et al. Clinical trials of improved ORS formulation: a review. WHO Bull.1994; 72: 945-55.

4. Table 1: Composition of standard and reduced osmolarity ORS solutions ORSStandardReduced Osmolarity ContentsmEq/L Glucose11175 Sodium9075 Chloride8065 Potassium20 Citrate10 Osmolarity311245 * 30 mmol/l of bicarbonate instead of 10 mmol/l of citrate

5. Randomized controlled trial… A no. of RCTs have been conducted comparing the standard (1975 WHO) and reduced-osmolarity (2002 WHO) solutions. In a trial of 300 adult patients with cholera, those who received low osm. ORS had no differences in stool output, duration of diarrhea, or need for unscheduled intravenous therapy compared with those treated with the standard WHO ORS.

6. RCTcont… Patients who received reduced-osmolarity ORS had an increased incidence of hyponatremia (serum sodium level <130 mmol/L) (odds ratio [OR], 2.1; 95% confidence interval [CI], 1.1-4.1). The mean difference in serum sodium at 24 hours of treatment between the 2 groups was 1.2 mEq/L, and none of the patients with hyponatremia in either group was symptomatic. Christopher et al, JAMA, 2004,291:2628-2631

7. WHO and UNICEF joint meet 2001 Among adults with cholera, clinical outcomes were not different among those treated with reduced-osmolarity ORS compared with standard ORS, although the risk of transient asymptomatic hyponatremia was noted Christopher et al, JAMA, 2004,291:2628-2631

8. WHO and UNICEF joint meet 2001 Further monitoring, including postmarketing surveillance studies, were strongly encouraged to better assess any risk of symptomatic hyponatremia in cholera-endemic parts of the world. World Health Organization. Reduced Osmolarity Oral Rehydration Salts (ORS) Formulation. New York, NY: UNICEF House; July 18, 2001 2001. WHO/FCH/CAH/01.22.

9. Concerns Pediatric and adult cholera patients typically lose 100 to 135 mEq of sodium per liter of diarrhea, respectively. The reduced-osmolarity solution with 75 mEq/L of sodium would therefore induce a negative sodium balance of ?25to ?60 mEq/L ingested when matching intake to output.

10. ConcernsCont…. Adult diarrhea rates in severe cholera approach 1 L/h, so losses of up to 300 mEq of sodium can accrue within 5 hours of such treatment, enough to sharply lower blood sodium levels. Even with antibiotics, oral maintenance usually lasts 24 to 44 hours in adult cholera patients, enough to induce massive sodium deficits using the low- sodium solution. Moreover, to expand intravascular volume rapidly, patients must drink more of a low-sodium solution, which may lead to fatigue and treatment failure. JAMA. 2004;291:2628-2631

11. ConcernsCont…. In malnourished patients with chronic hyponatremia and multiple diarrhea episodes, very low-sodium oral solutions (45 mEq/L) also aggravate hyponatremia (1 of 65 patients had seizure). Use of reduced-osmolarity solution in these patients should be relatively contraindicated, but the new recommendations do not address this point. JAMA. 2004;291:2628-2631.

12. ConcernsCont…. Another difficulty is that all studies of the new formulation involved single-incident diarrhea episodes. Where effective oral therapy programs exist, children may receive therapy for multiple diarrhea episodes. Surveys in several countries have shown more than 7 episodes of varied etiologies per child annually. The risk of aggravated hyponatremia might exist when such patients, already sodium depleted, present for treatment of incident episodes. This deserves study to determine the safety of low-sodium solutions in such patients. JAMA. 2004;291:2628-2631.

13. ConcernsCont…. Studies leading to the recommendation for the reduced- osmolarity ORS for noncholera diarrhea therapy had variable outcomes. Reduction in diarrhea rate, if real, is minimal; diarrhea duration is unaffected. The need for unscheduled intravenous fluids was not laboratory confirmed, and in the largest study it was not paralleled by reduced stool losses. For these reasons, and the risk of induction of hyponatremia, it remains unclear whether the new solution favorably alters the benefit-to-risk ratio for pediatric and adult diarrhea patients without cholera.

14. ConcernsCont…. Additional, more rigorous studies are needed to determine the optimal solution for such patients. What is clear is that the reduced-osmolarity ORS increases the risk for hyponatremia during therapy in adults with cholera but offers them no clinical advantages. Moreover, clinical findings in small numbers of pediatric patients with cholera were contradictory. JAMA. 2004;291:2628-2631.

15. Experience with Standard ORS The original WHO formulation with 90 mEq/L of sodium and 111 mmol/L of glucose proved a safe, effective formulation for all age groups and cholera or noncholera diarrhea. However, failure to communicate the information needed to ensure correct solution preparation, concentration, and appropriate drinking volumes can lead to electrolyte imbalance, whatever the formulation. Thus, inaccuracies in home-mixing of solutions led to hypernatremia in Egypt, a situation that was reversed with detailed instructions broadcast via television and taught in rehydration clinics. JAMA. 2004;291:2628-2631

16. Queries??? Should reduced osmolarity solution replace the current WHO oral rehydration solution as the new "standard" or should there be two standard solutions, one for regions where cholera is endemic and another for everywhere else?

17. Thank You