In a patient with anaphylaxis, is intramuscular (IM) epinephrine (adrenaline) or intravenous (IV) epinephrine preferred when there is no time difference for administration?

Intramuscular Epinephrine is Preferred for Anaphylaxis

Intramuscular (IM) epinephrine administered into the anterolateral thigh is the preferred route for anaphylaxis treatment, even when IV access is immediately available, because it is safer, easier to administer correctly, and has a more favorable risk-benefit profile than IV epinephrine. 1

Primary Route Selection

Intramuscular Administration is First-Line

• IM epinephrine is universally recommended as the initial treatment for anaphylaxis regardless of IV access availability. 1
• The American Heart Association gives IM epinephrine a Class 1 (strong) recommendation with the statement: "Epinephrine should be administered early by intramuscular injection (or autoinjector) to all patients with signs of a systemic allergic reaction, especially hypotension, airway swelling, or difficulty breathing." 1
• IM injection into the vastus lateralis (anterolateral thigh) achieves peak plasma concentrations in 8±2 minutes, which is rapid enough for effective anaphylaxis treatment. 1, 2

When IV Epinephrine May Be Considered

• IV epinephrine receives only a Class 2a recommendation (weaker evidence): "When an IV line is in place, it is reasonable to consider the IV route for epinephrine in anaphylactic shock, at a dose of 0.05 to 0.1 mg (1:10,000 concentration)." 1
• This lower recommendation class reflects the increased risk of dosing errors, cardiac complications, and the requirement for precise titration that IV administration demands. 1
• IV epinephrine should be reserved for refractory anaphylactic shock that does not respond to IM doses, or when continuous infusion is needed for protracted symptoms. 1

Safety Profile Comparison

IM Epinephrine Safety Advantages

• IM administration has a well-established safety profile with minimal risk of serious adverse effects when given at standard doses (0.3-0.5 mg for adults, 0.01 mg/kg for children). 1
• There are no absolute contraindications to IM epinephrine for anaphylaxis, including in patients with cardiac disease, elderly patients, or those on beta-blockers. 1, 2
• The risk of death from untreated anaphylaxis far exceeds any potential cardiac risk from appropriately dosed IM epinephrine. 1, 2

IV Epinephrine Risks

• IV administration carries significant risk of medication errors, particularly confusion between 1:1,000 and 1:10,000 concentrations, which can result in 10-fold overdosing and potentially fatal outcomes. 1, 2
• IV epinephrine can cause severe cardiac complications including ventricular arrhythmias, myocardial ischemia, and hypertensive crisis if not carefully titrated. 1
• The narrow therapeutic window with IV administration requires continuous cardiac monitoring and expertise in critical care dosing. 1

Practical Implementation

IM Administration Protocol

• Dose: 0.3-0.5 mg (0.3-0.5 mL of 1:1,000 solution) for adults; 0.01 mg/kg (maximum 0.3 mg) for children. 1
• Site: Anterolateral thigh (vastus lateralis muscle) with needle inserted at 90-degree angle. 1, 2
• Repeat: Every 5-15 minutes as needed if symptoms persist or recur. 1
• Can be administered through clothing if using an autoinjector, facilitating rapid treatment. 3

IV Administration Protocol (If Necessary)

• Only use when: IM epinephrine has failed to control symptoms after multiple doses, or patient is in profound refractory shock. 1
• Dose: 0.05-0.1 mg (5-10 mL of 1:10,000 solution) given as slow IV push, or continuous infusion at 5-15 μg/min. 1
• Requirements: Continuous cardiac monitoring, experienced personnel, and immediate availability of resuscitation equipment. 1

Evidence Quality Considerations

Supporting the IM-First Approach

• While no randomized controlled trials directly compare IM versus IV epinephrine in anaphylaxis (such trials would be unethical), decades of clinical experience and observational data consistently support IM as the safer initial route. 4, 5, 6
• One 2022 retrospective study of 142 anaphylaxis cases found that while CIV infusion was used in more severe cases, it required longer time to initiate treatment, suggesting IM should remain first-line for immediate administration. 7
• Delays in epinephrine administration are consistently associated with increased mortality and biphasic reactions, making the ease and speed of IM administration a critical advantage. 1, 3

Common Pitfalls to Avoid

• Never delay epinephrine while establishing IV access—give IM immediately upon recognizing anaphylaxis. 1, 3
• Avoid subcutaneous administration, which achieves peak levels in 34±14 minutes (versus 8±2 minutes for IM) and is inadequate for anaphylaxis. 2
• Do not use the deltoid muscle for IM injection—the vastus lateralis provides superior absorption. 1, 2
• Verify concentration before IV use—confusion between 1:1,000 and 1:10,000 solutions is a common fatal error. 2
• Do not withhold epinephrine due to concerns about cardiac disease—untreated anaphylaxis is far more dangerous. 1, 2