ESPE Abstracts (2016) 86 RFC10.4

Pharmacokinetics of Intravenous Glucagon in Children with Hyperinsulinaemic Hypoglycaemia

Pratik Shaha,b, Sofia Rahmana, Clare Gilbertb, Kate Morganb, Louise Hincheyb, Paul Bechc, Rakesh Amina,b & Khalid Hussaina,b

aUCL Institute of Child Health, London, UK; bGreat Ormond Street Hospital for Children, London, UK; cGut Hormone Laboratory, Imperial College London, London, UK

Background: Hyperinsulinaemic hypoglycaemia (HH) is one of the common causes of hypoglycaemia in infants and children. It can cause severe brain injury in children if not treated promptly. Diazoxide is first-line treatment for HH. Glucagon infusion is used in the management of children with HH. However it is unclear what dose of glucagon should be used in children.

Objective and hypotheses: To evaluate the efficacy, safety and pharmacokinetics of intravenous (IV) glucagon therapy in children with HH.

Method: Children admitted for management of HH in a tertiary hospital were included in the study. Plasma glucagon concentrations measured by radioimmunoassay (in pmol/l) were collected at times 0 min, +30 min, +60 min and +90 min after initiation of glucagon infusion (at 1 mcg/kg per hour; 2.5 mcg/kg per hour and 5 mcg/kg per hour respectively). Also, blood glucose was measured at the same times. Glucagon concentrations were checked for normality assumptions. Data was analysed using log transformation.

Results: A total of 12 were included in the study. Mean log glucagon (LnGlucagon) concentration at glucagon dose of 1 mcg/kg per hour (four patients), 2.5 mcg/kg per hour (four patients) and 5 mcg/kg per hour (four patients) were 3.296±0.448, 4.446±1.426 and 3.928±1.018 respectively, with an overall mean of 3.88±1.12. There was a significant difference in concentrations between the dose of 1 mcg/kg/hour with 2.5 and 5 mcg/kg per hour whereas no significant difference was observed between 2.5 and 5 mcg/kg per hour doses. LnGlucagon concentrations significantly increased with all three doses (P-value <0.001). There was a strong positive correlation (r=0.619, P-value=0.011) between glucagon dose 5 mcg/kg per hour and blood glucose concentrations.

Conclusion: This is the first study to measure plasma glucagon concentrations in response to an intravenous infusion of glucagon. This study shows that 2.5–5 mcg/kg per hour of IV glucagon can increase blood glucose levels significantly. These data will aid clinicians in the management of HH.

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