Pharmacokinetics of Intravenous Glucagon in Children with Hyperinsulinaemic Hypoglycaemia

Presentation Number: MON 600
Date of Presentation: April 3rd, 2017

Pratik Shah*1, Sofia A Rahman2, Clare Gilbert3, Kate Morgan3, Louise Hinchey3, Maria Guemes1, Paul Bech4, Rakesh Amin1 and Khalid Hussain5
1Great Ormond Street Hospital for Children and UCL Institute of Child Health, London, United Kingdom, 2UCL Great Ormond Street Institute of Child Health, London, 3Great Ormond Street Hospital for Children, London, United Kingdom, 4Imperial College London, London, United Kingdom, 5UCL Great Ormond Street Institute of Child Health, London, United Kingdom

Abstract

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 who are not responding to Diazoxide. 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.

Methods: 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 0min, +30min, +60min and +90min after initiation of glucagon infusion (at 1mcg/kg/hour; 2.5mcg/kg/hour and 5mcg/kg/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: 12 were included in the study. Mean log glucagon (LnGlucagon) concentration at glucagon dose of 1 mcg/kg/hour (4 patients), 2.5 mcg/kg/hour (4 patients) and 5 mcg/kg/hour (4 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/hour whereas no significant difference was observed between 2.5 and 5 mcg/kg/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 5mcg/kg/hour and blood glucose concentrations. None of the children were reported to have any side effects due to Glucagon.

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

 

Nothing to Disclose: PS, SAR, CG, KM, LH, MG, PB, RA, KH