When should epinephrine (adrenaline) be administered?

When to Give Epinephrine

Epinephrine should be administered immediately as first-line therapy once anaphylaxis is recognized or suspected, and promptly at the onset of cardiac arrest with no delay. 1

Anaphylaxis

Indications for Immediate Administration

• Epinephrine is the first-line treatment in all cases of anaphylaxis, with no substitute or alternative first-line medication 1
• Administer epinephrine as soon as possible once anaphylaxis is recognized, even if there is any doubt about the diagnosis 1
• Delays in instituting therapy with epinephrine are associated with increased risks of death and morbidity 1
• The benefits of epinephrine treatment far outweigh the risks of unnecessary dosing 1

Dosing and Administration for Anaphylaxis

• Adults and children ≥30 kg: 0.3 to 0.5 mg (0.3 to 0.5 mL of 1:1000 solution) intramuscularly into the anterolateral thigh every 5 to 10 minutes as necessary 2
• Children <30 kg: 0.01 mg/kg (0.01 mL/kg of 1:1000 solution), up to 0.3 mg (0.3 mL), intramuscularly into the anterolateral thigh every 5 to 10 minutes as necessary 2
• Intramuscular injection in the anterolateral thigh (vastus lateralis muscle) is preferred over subcutaneous injection as it provides more rapid increase in plasma and tissue concentrations 3
• When there is suboptimal response to the initial dose of epinephrine, or if symptoms progress, repeat epinephrine dosing remains first-line therapy over adjunctive treatments 1

Special Considerations in Anaphylaxis

• All patients at risk for anaphylaxis should carry two epinephrine autoinjectors and be trained in their use 4
• Schools present a special hazard for students with food allergies; epinephrine should be available for use by individuals trained to respond to such emergencies 1
• Patients with a history of severe anaphylactic reactions, particularly those with asthma, are at higher risk of fatal anaphylaxis and should have immediate access to epinephrine 1

Cardiac Arrest

Indications for Administration

• Epinephrine is the primary drug administered during cardiopulmonary resuscitation (CPR) to reverse cardiac arrest 5
• For cardiac arrest with a nonshockable rhythm (asystole, pulseless electrical activity), administer epinephrine as soon as feasible after the onset of arrest 1
• For cardiac arrest with a shockable rhythm (ventricular fibrillation, pulseless ventricular tachycardia), it may be reasonable to administer epinephrine after initial defibrillation attempts have failed 1

Dosing and Administration for Cardiac Arrest

• Adult dose: 1 mg IV/IO every 3-5 minutes during CPR 6, 7
• Pediatric dose: 0.01 mg/kg (0.1 mL/kg of 1:10,000 solution) IV/IO, with a maximum single dose of 1 mg 3
• Higher doses may not improve outcomes and can potentially be harmful 7

Timing Considerations in Cardiac Arrest

• Earlier administration of epinephrine in cardiac arrest is associated with improved outcomes compared to later administration 1, 7
• For nonshockable rhythms, administer epinephrine as soon as vascular access is established 1
• For shockable rhythms, focus on high-quality CPR and defibrillation as immediate priorities, with epinephrine typically administered after the third shock if defibrillation is unsuccessful 1

Common Pitfalls and Cautions

Dosing Errors

• Confusion about epinephrine dosing for different indications can lead to iatrogenic overdose 8
• Verify the correct concentration before administration: 1:1000 (1 mg/mL) for intramuscular use in anaphylaxis and 1:10,000 (0.1 mg/mL) for IV use in cardiac arrest 3
• Intravenous administration of the higher anaphylaxis concentration (1:1000) can cause severe cardiac complications 8

Route of Administration

• For anaphylaxis, the intramuscular route is preferred over subcutaneous for faster absorption 3
• For cardiac arrest, intravenous is the preferred route, but intraosseous is acceptable when IV access cannot be established quickly 3, 7
• IV administration of epinephrine for anaphylaxis should be reserved for cardiac arrest or severe shock unresponsive to intramuscular epinephrine and fluid resuscitation 3

Special Populations

• Patients with cardiovascular disease should still receive epinephrine for anaphylaxis, as the risk of a life-threatening anaphylactic reaction exceeds the risk of adverse effects 1
• Elderly patients and pregnant women may be at greater risk of developing adverse reactions when epinephrine is administered parenterally 9
• For pregnant patients with anaphylaxis or septic shock, life-sustaining therapy with epinephrine should not be withheld due to concerns about fetal effects 9

Institutional Preparedness

• Medical facilities should have established protocols to deal with anaphylaxis and cardiac arrest, with appropriate equipment readily available 1
• Epinephrine should be clearly packaged and labeled to avoid inappropriate usage and unnecessary complications 8
• Consider implementing prefilled and appropriately labeled intramuscular-dosed epinephrine syringes in crash carts that are easily distinguished from intravenous-dosed epinephrine syringes 8