Mortality impact of an increased blood glucose cut-off level for hypoglycaemia treatment in severely sick children aged 5 to 12 years in Malawi – an exploratory randomised controlled study

Low blood glucose concentration is a well-recognized risk factor for mortality in children admitted to hospitals in low-income settings. Current WHO guidelines define hypoglycaemia as a blood glucose level below 2.5 mmol/L; however, this threshold has been questioned. In a trial conducted in Malawian hospitals, increasing the treatment threshold to 5.0 mmol/L did not reduce in-hospital mortality among children aged 1 month to 5 years. The physiological response to low glucose and dextrose treatment in older children may differ yet remains understudied. This exploratory analysis was conducted to assess potential effects of dextrose treatment in severely ill children aged 5–12 years with blood glucose concentrations between 2.5 and 5.0 mmol/L. The study is an exploratory extension of a pragmatic randomised controlled trial where all eligible children were randomised to receive either a 5 ml/kg intravenous bolus followed by maintenance infusion of 10% dextrose (intervention group) or observation and standard care (control group). The primary outcome was in-hospital mortality; the secondary outcome was 24-hour mortality. Seventy-two children were enrolled with 36 allocated to each group. In-hospital mortality was 8% (3/36) in the intervention group and 19% (7/36) in the control group with an odds ratio (OR) for mortality of 0.8 (95% CI 0.46–2.25). The mortality after 24 h was 3% (1/36) in the intervention group and 8% (3/36) in the control group, with an OR of 0.4 (95% CI. 0.06–2.90). Adverse events occurred in 19% (7/36) in the intervention group and 39% (14/36) in the control group. This exploratory analysis suggests a potential reduction in mortality when intravenous dextrose treatment is administered to severely ill children aged 5–12 years who present to hospital with a low blood glucose. However, as the parent trial was powered for children less than 5 years the sample size for this older age group was insufficient to draw definitive conclusions. Larger, age-specific studies are warranted to determine the potential benefit of dextrose treatment in this population. The study is registered with ClinicalTrials.gov, NCT02989675 on 7th December 2016.