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Glucagon (GlucaGen, Gvoke)

Anesthesia Implications

Updated On: July 10, 2026

Classification:
Pancreatic hormone, hyperglycemic agent, antidote
Therapeutic Effects:
Hyperglycemia, positive inotropy, positive chronotropy, smooth muscle relaxation, GI motility inhibition
Time to Onset:

1-5 min

IM - 8-10 min

Time to Peak Effects:

5-20 min

Duration:

15-30 min (short — requires infusion for sustained effect in toxicity)

Primary Considerations:

Beta-Blocker Overdose - One of your go-to agents for refractory beta-blocker toxicity. Works by bypassing the beta receptor and stimulating adenylyl cyclase directly. Start with 3-5 mg IV bolus, follow with an infusion. Effects are transient — have vasopressors ready.

Calcium Channel Blocker Overdose - Similarly useful for calcium channel blocker (CCB) toxicity, though high-dose insulin therapy is now often preferred. Glucagon can be used as an adjunct when hemodynamics remain unstable.

Hypoglycemia - Classic reversal of severe hypoglycemia when IV access isn't available. IM or SC route works well in this setting. Give dextrose IV once access is established — glucagon effect is transient and depends on glycogen stores.

Glycogen Dependency - Glucagon only works if the patient has hepatic glycogen stores. It won't raise blood glucose in fasted, malnourished, or adrenally insufficient patients. Don't rely on it alone in these cases.

Nausea/Vomiting Risk - High rate of nausea and vomiting, especially with rapid IV push. Pre-treat with an antiemetic or push slowly when the clinical situation allows.

Radiology/Endoscopy Use - Used to relax smooth muscle of the GI tract during endoscopy or imaging procedures — reduces peristalsis and spasm.

Excessive Effect - Tachycardia and hypertension are transient and generally self-limiting. Rebound hypoglycemia is managed with IV dextrose.

Pediatric Implications - Dosing is weight-based for hypoglycemia (0.02-0.03 mg/kg IM/SC, max 1 mg). For beta-blocker toxicity, same principles apply with weight-based bolus dosing. Glycogen store dependency is a bigger concern in neonates and small infants.

Obstetric Implications - Limited data in pregnancy. Crosses the placenta minimally. Used for maternal hypoglycemia when IV access is unavailable. Generally considered safe for short-term use.

Contraindications:

Absolute:

Pheochromocytoma (can cause catecholamine release and severe hypertension)

Insulinoma (may cause rebound hypoglycemia)

Known hypersensitivity to glucagon

Relative:

Starvation, adrenal insufficiency, chronic hypoglycemia (reduced glycogen stores — limited efficacy)

Caution:

Patients on warfarin (enhanced anticoagulant effect with prolonged use)

Cardiovascular disease (tachycardia and hypertension)

IV push dose:

Hypoglycemia: 1 mg IV/IM/SC

Beta-blocker/CCB toxicity: 3-5 mg IV over 1 min; repeat 3 mg if no response in 10 min

IV infusion dose:

Beta-blocker/CCB toxicity: 1-5 mg/hr, titrated to hemodynamic response

IM dose:

Hypoglycemia: 1 mg IM (if no IV access)

Method of Action:

Binds glucagon receptors on hepatocytes -> activates adenylyl cyclase -> increases cAMP -> promotes glycogenolysis and gluconeogenesis. Cardiac glucagon receptors increase inotropy and chronotropy independent of beta-adrenergic stimulation.

Metabolism:

Hepatic and renal

Elimination:

Renal and biliary

Additional Notes:

Reconstitute lyophilized powder with provided diluent immediately before use; do not use saline for high-dose infusions (precipitation risk) — use D5W instead

Refrigerate; once reconstituted, use within 24 hours

Gvoke is a pre-filled auto-injector for SC use (emergency hypoglycemia kit)


Reference

Holger JS, et al. Insulin versus glucagon in beta-blocker overdose.J Med Toxicol. 2021;17(3):283-290.
Butterworth JF, Mackey DC, Wasnick JD. Morgan & Mikhail's Clinical Anesthesiology. 7th ed.McGraw Hill; 2022.
Rotella JA, et al. Treatment for beta-blocker poisoning: a systematic review.Clin Toxicol. 2020;58(10):943-983.
Hines RL, Marschall KE. Stoelting's Anesthesia and Co-Existing Disease. 8th ed.Elsevier; 2022.
American Heart Association. Cardiac arrest in special circumstances.Circulation. 2020;142(16 suppl 2):S366-S468.
Cole JB, Corcoran JN, Engebretsen KM, et al. Cardiovascular and adverse effects of glucagon for suspected beta-blocker toxicity. J Med Toxicol. 2022.link