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 2
- For adults, the standard dose is 0.3-0.5 mg; for children, it's 0.01 mg/kg 3
- 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 2
- Symptoms of severe or rapidly progressive anaphylaxis persist 2
- Initial symptoms resolve but then return (biphasic reaction) 2
- 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, 2
- Studies show that 8-28% of patients with anaphylaxis requiring treatment with epinephrine needed two or more doses 4
- Multiple observational studies demonstrate benefit for giving a second dose of epinephrine to patients not responding to a first dose 5
- 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 2
- This timeframe allows sufficient opportunity to evaluate the response to the initial dose while not delaying additional treatment if needed 2
Safety Considerations
- Pharmacologic effects of epinephrine include transient pallor, tremor, anxiety, and palpitations, which are similar to endogenous "fight or flight" responses 2
- Serious adverse effects of intramuscular epinephrine are rare, especially in children 2
- There is no absolute contraindication to epinephrine treatment in anaphylaxis 2
- 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, 2
- Place the patient on their back or in a position of comfort if there is respiratory distress and/or vomiting 2
- Elevate the lower extremities and do not allow standing, walking, or running 2
- Transport the patient to an emergency department for further assessment and monitoring 2
- All patients with anaphylaxis should be observed in a medical setting after symptom resolution due to the possibility of biphasic reactions 6
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 3
- Failing to recognize when a second dose is needed, particularly in severe or rapidly progressing anaphylaxis 2
- Administering epinephrine by incorrect routes (subcutaneous has delayed onset; intravenous increases risk of adverse effects) 7
- Accidentally injecting epinephrine into a finger, which can cause vasoconstriction and necrosis 3
- Extending observation periods unnecessarily for low-risk patients, as biphasic reactions typically occur either shortly after initial symptom resolution or many hours later 6