When do you administer a second dose of epinephrine (EpiPen) in an anaphylactic reaction?

When to Administer a Second Dose of Epinephrine (EpiPen) in Anaphylaxis

If a person with anaphylaxis does not respond to the initial dose of epinephrine and emergency medical services will exceed 5 to 10 minutes in arrival time, a repeat dose may be considered. 1

Initial Epinephrine Administration

• Epinephrine should be administered at the first sign of an anaphylactic reaction 1
• The first dose should be injected intramuscularly in the mid-outer aspect of the thigh using an autoinjector 1
• For adults, the standard dose is 0.3-0.5 mg; for children, it's 0.01 mg/kg 2
• First aid providers may assist a person experiencing anaphylaxis to use their autoinjector if assistance is required 1

Criteria for Administering a Second Dose

A second dose of epinephrine should be administered when:

• The person does not respond to the initial dose within 5-15 minutes 1
• Symptoms of severe or rapidly progressive anaphylaxis persist 1
• Initial symptoms resolve but then return (biphasic reaction) 1
• The emergency response system has been activated but arrival will exceed 5-10 minutes 1

Evidence Supporting Second Dose Administration

• Between 7% and 18% of people with anaphylaxis require more than one dose of epinephrine 1
• Studies show that 8-28% of patients with anaphylaxis requiring treatment with epinephrine needed two or more doses 3
• Multiple observational studies demonstrate benefit for giving a second dose of epinephrine to patients not responding to a first dose 1
• Most patients who received a second dose of epinephrine for anaphylaxis improved after administration 1

Timing of Second Dose

• The second dose should be administered 5 to 15 minutes after the first if symptoms persist or recur 1
• This timeframe allows sufficient opportunity to evaluate the response to the initial dose while not delaying additional treatment if needed 1

Safety Considerations

• Pharmacologic effects of epinephrine include transient pallor, tremor, anxiety, and palpitations, which are similar to endogenous "fight or flight" responses 1
• Serious adverse effects of intramuscular epinephrine are rare, especially in children 1
• There is no absolute contraindication to epinephrine treatment in anaphylaxis 1
• Patients who received a second dose of epinephrine were more likely to be admitted to the hospital, though this appeared to be due to severity of illness rather than adverse effects of epinephrine 1

After Epinephrine Administration

• Always activate emergency medical services for a person experiencing anaphylaxis 1
• Place the patient on their back or in a position of comfort if there is respiratory distress and/or vomiting 1
• Elevate the lower extremities and do not allow standing, walking, or running 1
• Transport the patient to an emergency department for further assessment and monitoring 1
• All patients with anaphylaxis should be observed in a medical setting after symptom resolution due to the possibility of biphasic reactions 4

Common Pitfalls to Avoid

• Delaying the administration of epinephrine, which can lead to increased risk of hospitalization and poor outcomes including hypoxic-ischemic encephalopathy and death 2
• Failing to recognize when a second dose is needed, particularly in severe or rapidly progressing anaphylaxis 1
• Administering epinephrine by incorrect routes (subcutaneous has delayed onset; intravenous increases risk of adverse effects) 5
• Accidentally injecting epinephrine into a finger, which can cause vasoconstriction and necrosis 2
• Extending observation periods unnecessarily for low-risk patients, as biphasic reactions typically occur either shortly after initial symptom resolution or many hours later 4