Metabolic acidosis during continuous glucagon therapy for neonatal hypoglycemia

Refractory neonatal hypoglycemia may be treated with glucagon infusions, which have been associated with thrombocytopenia and hyponatremia. After anecdotally noting metabolic acidosis during glucagon therapy in our hospital, an outcome not previously reported in the literature, we aimed to quantify occurrence of metabolic acidosis (base excess >-6) as well as thrombocytopenia and hyponatremia during treatment with glucagon.

We performed a single-centre retrospective case series. Descriptive statistics were used and subgroups compared with Chi-Square, Fisher's Exact Test, and Mann-Whitney U testing.

Sixty-two infants (mean birth gestational age 37.2 weeks, 64.5% male) were treated with continuous glucagon infusions for median 10 days during the study period. 41.2% were preterm, 21.0% were small for gestational age, and 30.6% were infants of diabetic mothers. Metabolic acidosis was seen in 59.6% and was more common in infants who were not born to diabetic mothers (75% versus 24% in infants of diabetic mothers, P<0.001). Infants with versus without metabolic acidosis had lower birth weights (median 2,743 g versus 3,854 g, P<0.01) and were treated with higher doses of glucagon (0.02 versus 0.01 mg/kg/h, P<0.01) for a longer duration (12.4 versus 5.9 days, P<0.01). Thrombocytopenia was diagnosed in 51.9% of patients.

In addition to thrombocytopenia, metabolic acidosis of unclear etiology appears to be very common with glucagon infusions for neonatal hypoglycemia, especially in lower birth weight infants or those born to mothers without diabetes. Further research is needed to elucidate causation and potential mechanisms.