Epinephrine Dosing Guidelines

Introduction to Epinephrine Dosing

• The American Heart Association recommends administering 1 mg IV/IO every 3-5 minutes for cardiac arrest, with evidence showing it improves return of spontaneous circulation (ROSC) without clear benefit for survival to discharge or neurologically intact survival 1, 2
• For anaphylaxis, the American Heart Association suggests giving 0.3-0.5 mg (1:1000) intramuscularly every 5-15 minutes, with IV dosing reserved for refractory shock or when IV access is already established 3, 4, 5

Cardiac Arrest Dosing

• The American Heart Association recommends a dose of 1 mg IV/IO (1:10,000 concentration) for adult cardiac arrest, with an interval of every 3-5 minutes during ongoing resuscitation 1, 2
• Early administration (within 1-3 minutes) of epinephrine is associated with improved ROSC, survival to discharge, and neurologically intact survival compared to delayed administration for nonshockable rhythms (asystole/PEA) 1, 2
• High-dose epinephrine (0.1-0.2 mg/kg) does not improve survival to discharge or neurological outcomes compared to standard dosing, and may increase ROSC but potentially worsens post-arrest outcomes 1, 2

Anaphylaxis Dosing

• The American Heart Association recommends intramuscular epinephrine into the anterolateral thigh as the first-line treatment for anaphylaxis, with a dose of 0.3-0.5 mg (1:1000 concentration) for adults and children ≥30 kg, and 0.01 mg/kg (1:1000 concentration) for children <30 kg 3, 4, 5
• The repeat interval for anaphylaxis dosing is every 5-15 minutes as needed for persistent symptoms 3, 4, 5
• For anaphylactic shock, IV epinephrine at dramatically lower doses than cardiac arrest is reasonable, with a bolus dose of 0.05-0.1 mg (50-100 mcg) using 1:10,000 concentration, and an infusion rate of 5-15 mcg/min (0.05-0.1 mcg/kg/min) 3, 4, 5, 6

Severe Asthma

• The American Heart Association does not recommend epinephrine for severe asthma exacerbations, instead recommending nebulized albuterol (2.5-5 mg in 3 mL saline, repeated as necessary) as the bronchodilator of choice 3, 7

Special Populations and Monitoring

• Close hemodynamic monitoring is mandatory for anaphylactic shock due to rapid cardiovascular changes 3, 4, 5
• Patients on beta-blockers may have refractory hypotension despite epinephrine, and may require glucagon 1-5 mg IV over 5 minutes followed by infusion (5-15 mcg/min) 1, 7, 6
• Pediatric dosing considerations include 0.01 mg/kg (0.1 mL/kg of 1:10,000) IV/IO every 3-5 minutes for cardiac arrest, and 0.01 mg/kg (0.01 mL/kg of 1:1000) IM every 5-10 minutes for anaphylaxis 7, 8, 6

Route-Specific Considerations

• Intramuscular injection into the vastus lateralis produces faster peak plasma concentrations than subcutaneous or deltoid injection, and avoids the risk of severe hypertension and cardiac complications from IV overdose 8, 3, 4, 5
• IV administration requires close monitoring due to the risk of extravasation and tissue necrosis, and antidotes such as phentolamine may be necessary in case of extravasation 8

Anaphylaxis and Cardiac Arrest Management with Epinephrine

Anaphylaxis Treatment

• For patients with anaphylaxis, the American Academy of Allergy, Asthma, and Immunology recommends IV epinephrine infusion at 5-15 mcg/min (0.05-0.1 mcg/kg/min), titrated to response, with mandatory continuous hemodynamic monitoring 9
• The American Academy of Allergy, Asthma, and Immunology suggests an alternative IV epinephrine preparation by adding 1 mg (1 mL of 1:1000) to 250 mL D5W for a 4 mcg/mL concentration, infused at 1-4 mcg/min initially, with a maximum of 10 mcg/min 10
• For adjunctive therapy, the American Academy of Allergy, Asthma, and Immunology recommends H1 antihistamine, such as diphenhydramine 25-50 mg IV/IM (1-2 mg/kg in children), never used alone but only after epinephrine administration 9, 10
• The American Academy of Allergy, Asthma, and Immunology also suggests H2 antihistamine, such as ranitidine 50 mg IV in adults, 1 mg/kg (12.5-50 mg) in children over 5 minutes, in combination with H1 antihistamine, which is superior to H1 alone but still second-line 9, 10

Cardiac Arrest Management

• For cardiac arrest caused by anaphylaxis, the American Heart Association recommends high-dose IV epinephrine with rapid escalation, starting with 1-3 mg (1:10,000) IV slowly over 3 minutes, followed by 3-5 mg IV over 3 minutes, and then 4-10 mg/min infusion 9
• The American Heart Association suggests that children with anaphylaxis-induced cardiac arrest should receive 0.01 mg/kg (0.1 mL/kg of 1:10,000) up to 10 mg/min infusion rate 9

Evidence‑Based Adrenaline Dosing for Anaphylaxis and Cardiac Arrest

Adult Anaphylaxis (Intramuscular)

• Initial dose: 0.3–0.5 mg of 1:1000 adrenaline (1 mg/mL) injected into the mid‑anterolateral thigh for patients weighing ≥ 30 kg. Repeat every 5–15 minutes if symptoms persist. Class I recommendation, high‑quality evidence 11

Pediatric Anaphylaxis (Intramuscular)

• Initial dose: 0.01 mg/kg of 1:1000 adrenaline (maximum 0.3 mg) injected into the anterolateral thigh. Repeat every 5–15 minutes as needed. Class I recommendation, high‑quality evidence 11

Adult Cardiac Arrest (Intravenous/Intra‑osseous)

• Standard dose: 1 mg of 1:10 000 adrenaline (0.1 mg/mL) administered IV or IO every 3–5 minutes during ongoing resuscitation. Class I recommendation, high‑quality evidence [11][12]
• Timing for non‑shockable rhythms (asystole/PEA): Give the first dose as soon as feasible after arrest recognition. Class I, high‑quality evidence 12
• Timing for shockable rhythms (VF/VT): Administer the first dose after initial defibrillation attempts have failed. Class I, high‑quality evidence 12

Pediatric Cardiac Arrest (Intravenous/Intra‑osseous)

• Standard dose: 0.01 mg/kg (0.1 mL/kg of 1:10 000 solution) IV/IO every 3–5 minutes, up to a maximum of 1 mg per dose. Class I, high‑quality evidence 13
• Refractory arrest: Consider higher doses of 0.1–0.2 mg/kg (using 1:1000 solution) for unresponsive asystole or PEA. Class IIb, moderate‑quality evidence 13

High‑Dose Epinephrine in Cardiac Arrest

• Not recommended: Routine use of >1 mg epinephrine does not improve survival to discharge or neurological outcome. Class III, high‑quality evidence 12

Transition from Anaphylaxis to Cardiac Arrest

• Protocol change: When a patient with anaphylaxis becomes pulseless, discontinue the 0.3–0.5 mg IM regimen and immediately start the cardiac‑arrest protocol of 1 mg IV/IO every 3–5 minutes. Class I, high‑quality evidence [13][11]
• Immediate action: Begin high‑quality CPR, obtain IV/IO access, and deliver 1 mg of 1:10 000 adrenaline as soon as access is secured. Class I, high‑quality evidence 13
• Escalated dosing for refractory anaphylactic arrest: Give 1–3 mg IV (1:10 000) over 3 minutes, followed by 3–5 mg IV over 3 minutes, then a continuous infusion of 4–10 mg/min if needed. Class IIa, moderate‑quality evidence 13

IV Adrenaline for Refractory Anaphylaxis

• Indication: Use IV adrenaline only when an IV line is already in place and the patient remains in anaphylactic shock despite multiple IM doses. Class I, high‑quality evidence 11
• Adult IV bolus: 50–100 µg (0.05–0.1 mg) of 1:10 000 adrenaline, titrated slowly to clinical response. Class I, high‑quality evidence 11
• Adult IV infusion: 0.05–0.1 µg/kg/min (≈1–4 µg/min, max 10 µg/min) using a 1:10 000 solution; continuous cardiac monitoring and frequent blood‑pressure checks are mandatory. Class I, high‑quality evidence 11

Severe Asthma Exacerbations

• Adrenaline not recommended: Use nebulized albuterol 2.5–5 mg in 3 mL saline (repeat as needed) as the bronchodilator of choice. Class III, moderate‑quality evidence 13

Patients Receiving Beta‑Blockers

• Potential refractoriness to adrenaline: Administer glucagon 1–5 mg IV over 5 minutes (20–30 µg/kg in children, max 1 mg), followed by an infusion of 5–15 µg/min. Class IIa, moderate‑quality evidence 13