What is the role of glucagon (Glucagon) in the treatment of anaphylaxis?

Glucagon for Anaphylaxis

Glucagon is a second-line agent reserved exclusively for patients on beta-blockers who develop anaphylaxis refractory to epinephrine and fluid resuscitation—it should never replace or delay epinephrine administration. 1, 2

Primary Treatment Remains Epinephrine

• Epinephrine 0.3-0.5 mg intramuscularly (1:1000 dilution) into the anterolateral thigh is the only first-line treatment for anaphylaxis and must be given immediately. 2, 3, 4
• Epinephrine can be repeated every 5-15 minutes as needed for persistent symptoms. 1, 2
• No other medication, including glucagon, has the life-saving pharmacologic effects across multiple organ systems (airway, cardiovascular, and mast cell stabilization) that epinephrine provides. 4, 5

Specific Indication for Glucagon

Glucagon is indicated only when:

• The patient is taking a beta-blocker (either selective or non-selective). 1, 2
• Anaphylaxis is refractory to multiple doses of epinephrine. 1
• Hypotension persists despite adequate fluid resuscitation (1-2 liters crystalloid for adults, 20 mL/kg boluses for children). 1

Dosing and Administration

• Adult dose: 1-5 mg IV administered over 5 minutes, followed by continuous infusion at 5-15 mcg/min (or mg/min per some sources) titrated to clinical response. 1, 2
• Pediatric dose: 20-30 mcg/kg (maximum 1 mg) IV over 5 minutes. 1, 2
• The mechanism involves bypassing beta-receptors to directly activate adenylyl cyclase, thereby increasing cardiac contractility and heart rate independent of beta-receptor stimulation. 1

Critical Precautions

• Aspiration risk: Glucagon commonly causes nausea and vomiting, so aspiration precautions must be observed during administration. 1
• Not a substitute: Glucagon does not replace epinephrine or standard therapies—it is purely supplemental in this specific clinical scenario. 6
• The evidence base for glucagon in anaphylaxis consists primarily of case reports and expert consensus rather than randomized trials. 7

Clinical Algorithm for Beta-Blocker Patients

1. Administer epinephrine IM immediately (0.3-0.5 mg for adults). 2, 3
2. Begin aggressive fluid resuscitation (1-2 L crystalloid bolus for adults). 1
3. Repeat epinephrine every 5-15 minutes if hypotension persists. 1, 2
4. If hypotension remains refractory after 2-3 doses of epinephrine and adequate fluids, administer glucagon 1-5 mg IV over 5 minutes. 1, 2
5. Follow with glucagon infusion at 5-15 mcg/min if initial bolus is effective. 1
6. Consider vasopressors (dopamine 2-20 mcg/kg/min or norepinephrine) if glucagon fails. 1

Common Pitfalls

• Never delay epinephrine: The most dangerous error is withholding or delaying epinephrine in favor of glucagon or other agents—this directly contributes to anaphylaxis fatalities. 3, 4, 5
• Don't use glucagon prophylactically: Glucagon has no role in preventing anaphylaxis or as first-line treatment in any patient, regardless of beta-blocker use. 6
• Recognize the limitation: Even in beta-blocker patients, epinephrine remains first-line because it still provides some benefit through alpha-adrenergic effects (vasoconstriction) and partial beta-receptor activation. 1

Adjunctive Therapies (After Epinephrine)

• H1-antihistamine (diphenhydramine 25-50 mg IV) and H2-antihistamine (ranitidine 50 mg IV) may be added but only after epinephrine. 1, 2
• Corticosteroids (methylprednisolone 1-2 mg/kg IV every 6 hours) are not effective acutely and do not reliably prevent biphasic reactions, but may be considered in severe cases. 1, 3
• Nebulized albuterol (2.5-5 mg) for persistent bronchospasm unresponsive to epinephrine. 1, 2