How soon can a second dose of epinephrine (EpiPen) be administered if symptoms persist after the initial injection?

Timing of Repeat Epinephrine Administration for Anaphylaxis

A second dose of epinephrine (EpiPen) should be administered 5 to 15 minutes after the first dose if anaphylaxis symptoms persist or worsen. 1

Indications for Repeat Epinephrine Dosing

• Repeat epinephrine doses are needed for severe or rapidly progressive anaphylaxis and for failure to respond to the initial injection 1
• Approximately 8-28% of patients with anaphylaxis require a second dose of epinephrine 2, 3
• Specific situations requiring a second dose include:
  • Inadequate response to the first dose 1
  • Delayed administration of the initial dose 1
  • Inadequate initial dosing 1
  • Administration through a suboptimal route 1

Risk Factors for Requiring Multiple Doses

Patients are more likely to need multiple doses of epinephrine if they have:

• History of previous anaphylaxis (2.5 times higher risk) 3
• Presence of flushing or diaphoresis (2.4 times higher risk) 3
• Dyspnea or respiratory distress (2.2 times higher risk) 3

Administration Protocol

Dosing by Age/Weight

• Adults and children ≥30 kg (66 lbs):

  • 0.3 to 0.5 mg (0.3-0.5 mL) of epinephrine 4
  • Typically delivered via 0.3 mg auto-injector 1

• Children <30 kg (66 lbs):

  • 0.01 mg/kg (0.01 mL/kg) of epinephrine 4
  • Maximum of 0.3 mg per injection 4
  • Typically delivered via 0.15 mg auto-injector for children weighing 15-30 kg 5

Administration Technique

• Inject intramuscularly into the mid-outer aspect of the thigh (vastus lateralis muscle) 1, 6
• Can be administered through clothing if necessary 4
• For children, hold the leg firmly in place to minimize risk of injection-related injury 4
• Do not administer repeated injections at the same site due to risk of tissue necrosis from vasoconstriction 4

Post-Administration Care

• Place the patient in a supine position or position of comfort if respiratory distress is present 1
• Elevate the lower extremities 1
• Do not allow standing, walking, or running (can worsen hypotension) 1
• Activate emergency response system (call 911/EMS) 1
• Transport to an emergency department for further assessment and monitoring 1
• Additional treatments may include supplemental oxygen, intravenous fluids, and other interventions 1

Common Pitfalls to Avoid

• Failure to administer epinephrine promptly has been repeatedly implicated in anaphylaxis fatalities 1
• Many patients and caregivers are not sufficiently skilled in using auto-injectors after only one instruction session 7
• Common errors include:
  • Failing to remove the safety cap before attempting injection 7
  • Not holding the auto-injector in place long enough 7
  • Using incorrect technique or injection site 6

Monitoring for Biphasic Reactions

• Biphasic anaphylaxis (recurrence after initial resolution) can occur 1
• Risk factors for biphasic reactions include:
  • Severe initial presentation 1
  • Requiring more than one dose of epinephrine 1
  • Wide pulse pressure 1
  • Unknown anaphylaxis trigger 1
  • Extended observation is recommended for patients with resolved severe anaphylaxis or those requiring multiple epinephrine doses 1

Remember that epinephrine is the first-line treatment for anaphylaxis, and there are no absolute contraindications to its use in this life-threatening condition 1.