Epipen as an Alternative to Glucagon in the Treatment of Hypoglycemia in Children With Diabetes

Abstract

OBJECTIVE -Fear of a severe hypoglycemic reaction is a major obstacle to achieving nearnormal plasma glucose levels. Although parenteral glucagon is effective in treating these reactions, it is cumbersome to use, causes severe nausea, and is impractical in the school setting. Epinephrine is available as a premixed injection (Epipen) that may be used by all care providers. Using Epipen to treat hypoglycemia may be an effective, safe, and easy-to-use alternative to glucagon.RESEARCH DESIGN AND METHODS -Ten children (age 11.7 Ϯ 2.4 years) with type 1 diabetes were studied on two occasions. After an overnight equilibration period, hypoglycemia was induced via an insulin pump (1 mU ⅐ kg -1 ⅐ min -1 ). At a blood glucose level of 2.8 mmol/l, either glucagon (1 mg) or epinephrine (0.3 mg), in random order, was administered intramuscularly and responses were monitored.RESULTS -Plasma free insulin concentrations were similar in both studies. Plasma glucose levels increased by 1.7 Ϯ 0.2 mmol/l (mean Ϯ SEM) in 10 min and by 2.6 Ϯ 0.2 mmol/l in 15 min with administration of glucagon and were not consistently increased with administration of epinephrine (P Ͻ 0.01). Peak glucagon concentrations after administration of glucagon were Ͼ60-fold higher than basal concentrations. After administration of epinephrine, peak epinephrine levels were 20-fold higher than basal concentrations.CONCLUSIONS -Epinephrine does not seem to be an adequate substitute for glucagon in the treatment of severe hypoglycemia. The effectiveness of glucagon in reversing hypoglycemia and its side effects of nausea and vomiting are likely related to the markedly supraphysiologic plasma levels achieved with the standard intramuscular dose. Diabetes Care 24:701-704, 2001S evere hypoglycemia is the most frequent and feared acute complication of treatment of type 1 diabetes during childhood. In fact, fear of a severe hypoglycemic reaction has become a major obstacle in achieving lower glycosylated hemoglobin levels with intensive treatment. Parenteral injection of 1.0 mg glucagon is the standard treatment for a severe insulin reaction (1,2), but the need to reconstitute the hormone with diluent makes it difficult to use in an emergent situation. In addition, the standard dose of glucagon is often associated with severe nausea and occasionally with vomiting, which can complicate recovery from hypoglycemia by limiting the patient's intake of oral carbohydrate. Because glucagon can only be administered by a licensed health professional in many school systems, diabetic children may be precluded from field trips and other extracurricular activities for reasons of safety.Even though stimulation of epinephrine secretion is one of the main endogenous hormonal defenses against insulininduced hypoglycemia in type 1 diabetes, use of epinephrine for treatment of severe hypoglycemia in children has not been tested. This is surprising because a premixed and prefilled injection system for parenteral epinephrine administration is available for treatment of severe allergic reac...

Treatment of insulin poisoning: A 100‐year review

“…Adrenaline was commonly used to treat insulin‐induced hypoglycaemia in the first decades of insulin therapy, including in cases of poisoning 24–26 . A small study in children with diabetes made hypoglycaemic by insulin injection found adrenaline injection (300 μg intra‐muscularly) to be ineffective in restoring blood glucose concentration 27 . The β 2 ‐adrenergic agonist terbutaline increased blood glucose concentration in hypoglycaemic experimental subjects with Type 1 diabetes, but not in those with normal insulin secretion, and it was less effective than glucagon 28 …”

Toward Closing the Loop: An Update on Insulin Pumps and Continuous Glucose Monitoring Systems

“…This therapy, of course, depends on the patient having adequate glycogen stores. Epinephrine has also been tried in the treatment of hypoglycemia, but was relatively ineffective 31. Amylin, or islet amyloid polypeptide, can also be added to delay gastric emptying resulting in a slower rate of glucose change following a meal, since meals with their rapid rate of change present the greatest challenge to a SQ insulin/SQ sensor closed loop.…”

Kann die niedrig dosierte subkutane Glukagon-Gabe schwere Hypoglykämien bei Typ-1-Diabetes im Kindesalter verhindern und die Hospitalisationsrate senken?

“…Klinisch werden allerdings immer wieder Bauchschmerzen, Übelkeit und Erbrechen beschrieben (laut Novo-Nordisk in < 1 / 10 000 Fällen), die bei Dosen über 1 mg oder bei rascher Injektion (< 1 Minute) auftreten [10,36,37]. Eigene klinische Erfahrungen bestätigen dies [38], insbesondere eine erhöhte Rate an Erbrechen nach zu schneller Injektion und Erreichen erhöhter Plasmaspiegel durch Hilfspersonen unter Stress [11]. Unklar ist, ob die beschriebenen Nebenwirkungen nur dem Glukagon zuzuschreiben sind oder auch als Symptom der Hypoglykämie gewertet werden kön-nen.…”

“…Glukagon als Notfallmedikation bei Hypoglykä-mie sollte bereits in jedem T1DM-Haushalt vorhanden sein. Es ist bislang als "letzte" Möglichkeit in hoher Dosierung mit Nebenwirkungen, insbesondere Erbrechen, behaftet [11]. Die niedrig dosierte Glukagongabe könnte unter Berücksichtigung der spezifischen Indikation und ergänzend zu den bisherigen Therapiemaßnahmen nebenwirkungsarm helfen, wiederholt niedrige Werte bei hypoglykämischen Episoden im Rahmen von Infekten zu behandeln [38 -40, 42].…”

“…Zusätzlich können Helfer vor Ort bei schwerer Hypoglykämie Glukagon subkutan oder intramuskulär applizieren [10]. Gleichwertige medikamentöse Alternativen zu Glukagon sind nicht verfügbar [11]. Abstract !…”