Background: Severe-persistent hypoglycaemia (SPH) in congenital hyperinsulinism (HI) can cause blindness and brain damage. First line treatment with diazoxide treatment can cause significant side effects, including fluid retention. Off-label use of i.v. reconstituted glucagon is also used but little safety and efficacy data have been reported.
Objective and hypotheses: To evaluate the use of i.v. glucagon infusion for management of SPH in HI.
Method: Anonymised data regarding age, duration, dose, responsiveness, and adverse events was collected retrospectively from three international HI centres, although not consistently. The duration of treatment was short-term (<14 days) or long-term (>14 days). Responsiveness was defined as reduction in glucose infusion rate (GIR) by 50% or achievement of euglycaemia (plasma glucose >3.5 mmol/l (63 mg/dl)), or a twofold increase in plasma glucose following an i.v. bolus of glucagon.
Results: Information available in 135 patients with HI was collated. In one centre, 12 patients were treated short-term pre-operatively. Glucagon decreased GIR from 19.7 to 7 mg/kg per min in nine children of median (range) age 17.5 days (3665) and weight 4.3 kg (2.610.3) Eight patients with transient HI due to perinatal stress were also treated at age 5 days (210) and birth-weight 3.1 kg (2.43.5) for a duration of 7 days (213) to achieve euglycaemia. Treatment complications included i.v. line occlusion due to glucagon precipitation in seven of 20 children. In other centres, a total of 115 children were treated with i.v. glucagon long-term pre-operatively, the duration of treatment varying between 2 and 6 weeks, with good response noted in 109 children, partial response in five children and one being non-responsive. One child developed severe diarrhoea, while two developed necrolytic migratory erythema as adverse events.
Conclusion: I.v. glucagon therapy has been used effectively in short- and long-term treatment in 135 patients with HI. Severe drug reactions from prolonged use are few. Short-term complications included i.v. line occlusion from precipitation of reconstituted glucagon in 33% of those in whom data was available.
Declaration of interest: J Kinzel works for Xeris, a company developing a form of soluable Glucagon and P Thornton has performed consulting work for Xeris Pharmaceuticals.
01 Oct 2015 - 03 Oct 2015