Anaphylaxis Treatment Protocol

Immediate Administration

• The American College of Allergy, Asthma, and Immunology recommends injecting 0.3 mg epinephrine intramuscularly into the anterolateral thigh immediately upon recognition of anaphylaxis, and repeat every 5 minutes as needed until symptoms resolve 1
• The injection can be administered through clothing if necessary—do not delay for clothing removal 2
• The lateral thigh site achieves peak plasma concentrations in 8±2 minutes compared to 34±14 minutes with subcutaneous deltoid injection 1, 2

Dosing Parameters

• For patients ≥25 kg (55 lbs): Use 0.3 mg EpiPen (adult dose) 2
• For patients 10-25 kg: Use 0.15 mg EpiPen Jr 2
• The standard dose is 0.01 mg/kg, with a maximum single dose of 0.5 mg for adults 1

Repeat Dosing Protocol

• Approximately 10-28% of patients require a second dose, and some require more 1
• The 5-minute interval can be liberalized to permit more frequent injections if the clinical situation demands it 3, 1
• Continue dosing based on clinical response rather than an arbitrary maximum number 1

Concurrent Emergency Management

• Call 911 or activate the resuscitation team immediately—do not wait to see if epinephrine works 1
• Position the patient supine with legs elevated 1
• Never allow the patient to stand or walk, as upright positioning increases mortality risk 1
• Administer oxygen at 6-8 L/min 3
• Establish IV access and prepare for fluid resuscitation 3

Fluid Resuscitation for Hypotension

• Administer normal saline bolus of 1000-2000 mL for adults (5-10 mL/kg in first 5 minutes) 3, 1
• Children may require up to 30 mL/kg in the first hour 3
• Large volumes of crystalloid may be necessary—some patients require 1-2 L rapidly 3

Escalation for Severe/Refractory Cases

• If the patient fails to respond to multiple IM doses (typically 2-3 injections), transition to IV epinephrine infusion 1, 4
• Preparation: Add 1 mg (1 mL) of 1:1000 epinephrine to 250 mL D5W to yield 4.0 mcg/mL concentration 3, 4
• Starting infusion rate: 1-4 mcg/min (15-60 drops/min with microdrop apparatus) 3, 4
• Titrate up to maximum of 10 mcg/min based on clinical response 3, 1, 4

Adjunctive Therapies (Secondary to Epinephrine)

• H1 antihistamine: Diphenhydramine 25-50 mg parenterally 1
• H2 antihistamine: Ranitidine 50 mg IV over 5 minutes or famotidine 1
• Corticosteroids: Hydrocortisone for severe cases (does not affect acute phase but may prevent biphasic reactions) 1

Post-Treatment Management

• Transport all patients to the emergency department via EMS for observation, even if symptoms completely resolve after epinephrine 1
• Observation period required: Biphasic reactions can occur up to 72 hours later (mean 11 hours) 2
• Prescribe two 0.3 mg epinephrine autoinjectors for home use with proper instruction 1
• Refer to allergist-immunologist for follow-up and identification of trigger 1

Critical Safety Points

• There is no absolute contraindication to epinephrine use in anaphylaxis—even in elderly patients or those with cardiac disease, the risk of death from untreated anaphylaxis far exceeds the risk of epinephrine-related adverse effects 3, 1, 2

Epinephrine Dosing and Administration in Anaphylaxis

Dosing Recommendations

• Adults (≥50 kg): Administer 0.3–0.5 mg of 1:1000 epinephrine intramuscularly; the maximum single dose is 0.5 mg. [5][6]
• Children (weight‑based): Give 0.01 mg/kg of 1:1000 epinephrine intramuscularly (≈0.01 mL/kg); the dose should not exceed 0.3 mg in prepubertal patients. [5][6]

Injection Technique

• Preferred site: The mid‑outer thigh (vastus lateralis muscle) is the only acceptable first‑line injection location. 5
• Pharmacokinetics: Intramuscular thigh injection achieves peak plasma epinephrine concentration in 8 ± 2 minutes, whereas subcutaneous deltoid injection peaks at 34 ± 14 minutes and is therefore too slow for emergency treatment. 5

Repeat Dosing Protocol

• Interval: If symptoms persist, repeat the intramuscular dose every 5–15 minutes as needed. 6
• Flexibility: The 5‑minute interval may be shortened in severe clinical situations. 6

Immediate Supportive Measures

• Patient positioning: Place the patient supine with legs elevated unless they have respiratory distress or are vomiting. 5
• Avoid upright posture: Standing, walking, or running increases mortality risk in anaphylaxis. 5
• Oxygen therapy: Provide supplemental oxygen at 6–8 L/min while epinephrine is being administered. 6

Fluid Resuscitation

• Adults: Give a normal‑saline bolus of 1 000–2 000 mL (equivalent to 5–10 mL/kg) within the first 5 minutes. 6
• Children: Administer up to 30 mL/kg of normal saline during the first hour of treatment. 6

Adjunctive Pharmacologic Therapy (Second‑Line)

• H1 antihistamine: Diphenhydramine 25–50 mg IV/IM (or 1–2 mg/kg in children) may be used for urticaria after epinephrine, but must never replace epinephrine. 6

Discharge Planning

• Written emergency action plan: Provide a patient‑specific anaphylaxis action plan that outlines symptom recognition, trigger avoidance, and epinephrine use instructions. 5

Epinephrine‑Centric Management of Acute Anaphylaxis in the Emergency Department

First‑Line Intramuscular Epinephrine

• Administer intramuscular epinephrine immediately—0.3–0.5 mg (1 mg/mL) for adults and adolescents ≥50 kg, or 0.01 mg/kg (maximum 0.3 mg) for children <50 kg—into the mid‑outer thigh (vastus lateralis). This is the sole first‑line therapy and must not be delayed for any other intervention. 7
• Autoinjector dosing: 0.15 mg for children weighing 10–25 kg, 0.3 mg for patients ≥25 kg, and 0.1 mg for infants when available (if not, 0.15 mg is acceptable for infants >7.5 kg). [7][8]

Repeat Dosing and Escalation to Intravenous Epinephrine

• If symptoms persist or recur, repeat intramuscular epinephrine every 5–15 minutes; intervals may be shortened in severe cases. 7
• Transition to intravenous epinephrine when the patient fails to respond after 2–3 intramuscular doses (approximately 10 minutes of treatment). 9

Intravenous Epinephrine Bolus Protocol

9

• After each bolus, repeat every 2 minutes if the response is inadequate, with continuous cardiac monitoring. 9

Intravenous Epinephrine Infusion

• Initiate infusion with a concentration of 4 µg/mL (add 1 mg epinephrine to 250 mL D5W).
• Start at 1–4 µg/min (≈15–60 mL/h) and titrate up to a maximum of 10 µg/min (≈600 mL/h) based on blood pressure, heart rate, and oxygenation. 7
• Weight‑based alternative: 0.05–0.1 µg/kg/min. 9

Alternative Vasopressors for Refractory Hypotension

• Vasopressin: 1–2 IU bolus, then infusion at 2 IU/hour. 9
• Norepinephrine: Infusion at 0.05–0.5 µg/kg/min. 9

Fluid Resuscitation in Hypotensive Anaphylaxis

• Give normal‑saline boluses of 1,000–2,000 mL (5–10 mL/kg) to adults within the first 5 minutes; children may receive up to 30 mL/kg in the first hour.
• Repeat boluses as needed, up to a cumulative 20–30 mL/kg, guided by clinical response. 9

Risk of Delayed Deterioration and Biphasic Reactions

• In a prospective Australian emergency‑department cohort, 17 % of anaphylaxis patients experienced delayed deterioration; 53 % of those required epinephrine, and 69 % of the repeat doses occurred within 4 hours of the initial reaction. 7
• Delayed administration of epinephrine or inadequate initial dosing are independent risk factors for delayed deterioration and biphasic reactions. 7

Tryptase Monitoring for Diagnostic Confirmation

• First serum tryptase sample: 1 hour after symptom onset.
• Second sample: 2–4 hours after onset.
• Baseline (reference) sample: ≥24 hours after the reaction. 9

Safety Priorities and Contraindications

• No absolute contraindications exist for epinephrine in anaphylaxis, even in elderly patients with cardiovascular disease; the mortality risk from untreated anaphylaxis outweighs any potential epinephrine‑related risk. 7
• Delayed epinephrine administration is directly associated with anaphylaxis‑related fatalities; epinephrine must be given before any other actions such as calling emergency services. 8