Common and Uncommon Usages of Glucagon in the Field (Part 1)

In the pre-hospital setting, Glucagon primarily plays a role in the management of hypoglycemic patients. Emergency Medical Technicians carry Glucagon as an alternative or adjunctive therapy to dextrose administration in these patients. However, this is not the only usage of Glucagon in the field. Many ALS protocols include Glucagon for the treatment of symptomatic bradycardia in patients who have overdosed on β-blockers or are refractory to standard ACLS treatments. As we will find, there are a number of alternative usages of Glucagon which could be considered in the field under online medical direction.

Common Clinical Applications of Glucagon

• Hypoglycemia
• Symptomatic bradycardia secondary to β-blocker overdose
• Symptomatic bradycardia secondary to Ca-channel blocker overdose

Uncommon Clinical Applications of Glucagon

• Steakhouse syndrome
• Refractory anaphylaxis
• Severe asthma (little support)
• Refractory CHF (little support)

Pharmacology

Glucagon is a hormone produced by alpha cells in the islets of Langerhans of the pancreas. The primary effect of Glucagon is to promote the release of stored glucose in the liver and stimulate the release of insulin from the pancreas to promote uptake of glucose into the cells. Additional effects of Glucagon include a cascade of activations resulting in an increase of cyclic-AMP (cAMP). cAMP is an important intracellular messenger, responsible for carrying the signals of epinephrine and glucagon across the cell membrane. cAMP also regulates the flux of Ca2+ through ion channels independent of β-adrenergic receptors. This quality of Glucagon is what is thought to explain the various changes to the cardiovascular system seen after its administration.

In the field, Glucagon is commonly packaged as a powder which is reconstituted with either sterile water or D5W (5% dextrose in water) to give a final concentration of 1 mg in 1 cc. Glucagon can be administered intravenously (IV), intraosseously (IO), intramuscularly (IM), subcutaneously (SQ), or intranasally (IN). Glucagon is assigned to the pregnancy category B, therefore usage during pregnancy should be considered when the benefits outweigh the potential risks. The most common side effects are nausea and vomiting, thought to be associated with the rate of IV administration. When giving high doses of Glucagon, the usage of antiemetics such as ondansetron or promethazine should be considered. Additionally some diluents packaged with Glucagon contain phenol, which in high doses can be toxic. Therefore, reconstitution should be done in sterile water, D5W, or normal saline.

Hypoglycemia

As this article is intended for pre-hospital providers, it is assumed that the usage of Glucagon in hypoglycemia is well understood, therefore this indication will not be explored in depth. However, pre-hospital providers may be surprised to learn that the administration of 2 mg Glucagon intranasally (IN) was shown to be as safe and efficacious as an IM administration of 1 mg. Recently the administration of drugs through the IN route has gained in popularity, the most visible of those being naloxone (Narcan). In 2009, naloxone administration via the IN route was added to the scope of practice for all levels of EMTs in North Carolina, where this author practices.

Given the few side effects and complications associated with the administration of Glucagon, it would be a powerful addition to BLS providers for hypoglycemic patients in which oral glucose is not indicated. Yet the widespread adoption of intranasal Glucagon has not been seen in EMS, even though studies on intranasal Glucagon were conducted as far back as the 1980s. One potential explanation could be the relatively high cost of Glucagon. A casual and unscientific search of Internet distributors shows the average price of 1 mg Glucagon ranges from $70-150 USD. In comparison, naloxone ranges from $18-25 USD for the common pre-hospital packaging. Given the economic troubles in 2009 and 2010, it seems unlikely that the intranasal route will gain traction amongst already cash strapped BLS providers.

Symptomatic Bradycardia

Beyond hyperglycemic effects, Glucagon exerts both positive chronotropic and inotropic effects on the heart through non-adrenergic receptors. Because the cardiovascular actions are orthogonal to β-adrenergic receptors, it should be considered in any symptomatic bradycardia refractory to sympathomimetics or as an adjunct to sympathomimetic therapy. High-dose IV Glucagon has been shown to be effective when there is a known β-blocker or Ca-channel blocker overdose.

The first consideration for EMTs when using Glucagon for a patient with suspected β-blocker or Ca-channel blocker overdose is the extreme dosage to be administered. A loading dose of 2-10 mg is cited by the literature, followed by 1-5 mg/hr maintenance infusions titrated to effect if hypotension and bradycardia persist. The service at which the author works only carries two 1 mg Glucagon kits per ambulance, which is relatively common amongst ALS providers. Therefore, a second unit or ALS QRV should be requested for an intercept to supply additional Glucagon kits. This logistical concern obviates any on-scene treatment with Glucagon for symptomatic bradycardia, and should not delay safe and expeditious transport.

In part 2, we'll explore some less traditional usages of Glucagon in the field.

References

• Pollock CV: Utility of Glucagon in the Emergency Department. J Emerg Med 1993; 11: 195-205.
• Rosenfalck AM, et al: Nasal glucagon in the treatment of hypoglycaemia in type 1 (insulin-dependent) diabetic patients. Diabetes Research and Clinical Practice 1992; 17: 43-50.
• Love JN, Howell JM: Glucagon Therapy in the Treatment of Symptomatic Bradycardia. Ann Emerg Med January 1997; 29:181-183.
• American Heart Association. Part 7.3: Management of Symptomatic Bradycardia and Tachycardia. Circulation 2005; 112; IV-67-IV-77.