Low-osmolarity oral rehydration solution for childhood diarrhoea: A systematic review and meta-analysis

Background: Oral rehydration solution (ORS) is crucial in the management of diarrhoea. Until the early 2000s, the standard formulation of glucose-based ORS with a total osmolarity of 311 mmol/L was being used for this purpose. However, due to concerns about sodium levels and cases of hypernatremia, a low-osmolarity ORS solution (LORS) with an osmolarity of 245mmol/L or less was developed to replace the standard ORS. With this systematic review, we aimed to assess the effectiveness of LORS compared to standard ORS for the treatment of acute and persistent diarrhoea. Methods: We comprehensively searched PubMed, CINAHL, the Cochrane Library, ClinicalTrials.gov, the World Health Organization (WHO) International Clinical Trials Registry Platform, and Scopus until 20 July 2023 for studies published after 1990 assessing the efficacy of LORS in acute and persistent diarrhoea in children under 10 years of age. Meta-analysis was conducted using the RevMan software. We performed log approximation for all the values for an outcome when studies reported arithmetic and geometric means per the Cochrane Handbook. We otherwise used the Cochrane Risk of Bias II tool to assess the risk of bias in individual studies, and assessed the quality of evidence using the Grading of Recommendations, Assessment, Development, and Evaluations approach. This review was commissioned by the WHO for revision of guidelines for childhood diarrhoea. Results: For the comparison of LORS to standard ORS in acute diarrhoea, our findings suggest that there was a significant decrease in the duration of diarrhoea (mean difference (MD) = -0.28; 95% confidence interval (CI) = -0.41, -0.15; moderate certainty of evidence), stool output (MD = -0.25; 95% CI = -0.35, -0.16; very low certainty of evidence), and ORS intake (MD = -0.18; 95% CI = -0.28, -0.07; moderate certainty of evidence) in patients receiving LORS. There was a comparable effect on the number of patients cured within five days, treatment failure, and frequency of unscheduled intravenous therapy (risk ratio (RR) = 0.77; 95% CI = 0.72, 9.38; low certainty of evidence). For persistent diarrhoea, there was a significant decrease in duration of diarrhoea (MD = -30.60; 95% CI = -48.95, -12.25), stool output (MD = -14.00; 95% CI = -26.63, -1.37), and ORS intake (MD = -21.40; 95% CI = -41.01, -1.79), while there was a comparable effect on the number of patients cured. Conclusion: Our findings suggest that LORS should continue to be recommended in children under the age of 10 years with acute watery or persistent diarrhoea and upholds the current WHO recommendations. Registration: PROSPERO: CRD42023438762.