What is the recommended emergency department management for an acute allergic reaction, including first‑line intramuscular epinephrine dosing for adults and children, airway support, adjunctive antihistamine and corticosteroid therapy, monitoring, and discharge planning?

Emergency Department Management of Acute Allergic Reactions

Intramuscular epinephrine 0.3–0.5 mg (adults) or 0.01 mg/kg (children, max 0.3 mg) injected into the mid-anterolateral thigh is the only first-line treatment for anaphylaxis and must be administered immediately—all other interventions are adjunctive and must never delay epinephrine. 1, 2

Immediate First-Line Treatment: Epinephrine

Dosing and Administration

• Adults and adolescents ≥50 kg: Administer 0.3–0.5 mg of 1:1000 (1 mg/mL) epinephrine intramuscularly into the mid-outer thigh (vastus lateralis). 1, 2

• Children <50 kg: Give 0.01 mg/kg of 1:1000 epinephrine intramuscularly (maximum 0.3 mg in prepubertal children). 1, 2

• Autoinjector dosing:

  • 0.15 mg for children 10–25 kg
  • 0.3 mg for patients ≥25 kg
  • 0.1 mg for infants where available (if unavailable, 0.15 mg is acceptable for infants >7.5 kg) 1

Why the Thigh?

• Intramuscular injection in the anterolateral thigh achieves peak plasma concentration in 8±2 minutes compared to 34±14 minutes with subcutaneous deltoid injection—this speed difference can be lifesaving. 2, 3

• The injection can be administered through clothing if necessary; do not delay for clothing removal. 2

Repeat Dosing Protocol

• Repeat epinephrine every 5–15 minutes if symptoms persist or recur. 1, 2

• Approximately 10–28% of patients require a second dose, and some require more. 2

• The 5-minute interval can be shortened if the clinical situation demands more frequent dosing. 2

• There is no maximum number of doses—continue based on clinical response rather than an arbitrary limit. 2

Concurrent Emergency Actions (Do Not Delay Epinephrine)

Immediate Steps

• Call 911 or activate the resuscitation team immediately—do not wait to see if epinephrine works. 2, 4

• Position the patient supine with legs elevated (unless respiratory distress or vomiting precludes this). 2, 4

• Never allow the patient to stand or walk—upright positioning increases mortality risk through cardiovascular collapse. 2, 4

• In pregnant patients, perform left uterine displacement to avoid aortocaval compression. 4

Airway and Breathing Support

• Administer 100% oxygen at 6–8 L/min for any patient with respiratory symptoms or who required multiple epinephrine doses. 2, 4

• For severe oropharyngeal/laryngeal edema where intubation may be impossible, prepare for emergency cricothyroidotomy and involve a provider with advanced airway expertise immediately. 4

• For persistent bronchospasm after epinephrine: Administer nebulized albuterol 2.5–5 mg in 3 mL saline—but recognize this does not treat airway edema or cardiovascular collapse. 2, 4

Fluid Resuscitation for Hypotension

Aggressive Crystalloid Administration

• Adults: Administer normal saline bolus of 1,000–2,000 mL (5–10 mL/kg) within the first 5 minutes. 2, 4

• Children: Give up to 30 mL/kg of normal saline in the first hour. 2, 4

• Repeat boluses as needed up to 20–30 mL/kg based on clinical response—large volumes may be necessary due to profound vasodilation and capillary leak. 1, 2

• Establish IV access immediately while administering epinephrine, but never delay epinephrine to obtain IV access. 2, 4

Management of Severe/Refractory Anaphylaxis

When to Escalate to IV Epinephrine

• If the patient fails to respond to 2–3 intramuscular doses (typically after 10 minutes of treatment), transition to IV epinephrine. 1, 2

IV Epinephrine Bolus Dosing

• Grade II reactions: 20 μg IV bolus 1

• Grade III reactions: 50–100 μg IV bolus 1

• Grade IV reactions (cardiac arrest): 1 mg IV, repeat per advanced life support guidelines 1

• Use only 1:10,000 concentration (0.1 mg/mL) for IV administration—using 1:1000 concentration can cause fatal arrhythmias. 4

• Repeat every 2 minutes if inadequate response, with continuous cardiac monitoring. 1

IV Epinephrine Infusion

• Preparation: Add 1 mg (1 mL of 1:1000) epinephrine to 250 mL D5W to yield 4.0 μg/mL concentration. 2, 3

• Starting rate: 1–4 μg/min (equivalent to 15–60 mL/hour). 2, 3

• Titrate up to maximum of 10 μg/min (600 mL/hour) based on blood pressure, heart rate, and oxygenation. 1, 2

• Alternatively: 0.05–0.1 μg/kg/min for weight-based dosing. 1, 4

Alternative Vasopressors for Refractory Hypotension

• Vasopressin: 1–2 IU bolus, followed by infusion at 2 IU/hour 1

• Norepinephrine: Infusion at 0.05–0.5 μg/kg/min 1

• Glucagon (for patients on β-blockers): 1–2 mg IV over 5 minutes (20–30 μg/kg in children, max 1 mg), followed by infusion of 5–15 μg/min—be aware of possible vomiting. 4

Adjunctive Therapies (Second-Line Only—Never Replace Epinephrine)

H1 Antihistamines

• Diphenhydramine 25–50 mg IV/IM (or 1–2 mg/kg in children) for urticaria and itching only. 2, 4

• Critical caveat: Antihistamines do not relieve stridor, bronchospasm, gastrointestinal symptoms, or shock—they treat only cutaneous symptoms. 2, 4

• Alternative: Cetirizine 10 mg orally (less sedating, second-generation). 4

H2 Antihistamines

• Ranitidine 50 mg IV over 5 minutes or famotidine 20 mg IV in adults. 2, 4

• May be added to H1 blocker, but evidence of benefit is minimal. 4

Corticosteroids

• Not recommended for acute anaphylaxis treatment—they have a slow onset (4–6 hours) and no proven benefit in the acute phase or in preventing biphasic reactions. 2, 4

• If administered empirically: Methylprednisolone 1–2 mg/kg/day IV every 6 hours or hydrocortisone 200 mg IV (adults), recognizing the weak evidence base. 2, 4

• The 2020 anaphylaxis practice parameter emphasizes that understanding of anaphylaxis pathophysiology reinforces why epinephrine is first-line while antihistamines and glucocorticoids are solely second-line. 1

Post-Treatment Monitoring and Observation

Observation Duration

• Minimum 4–6 hours of observation in a facility equipped to manage anaphylaxis after complete symptom resolution. 2, 4

• Extended observation (≥6 hours) or admission is required for:

  • Patients who received >1 epinephrine dose (strongest predictor of biphasic reaction) 4
  • Severe initial presentation (hypotension, respiratory compromise) 4
  • Wide pulse pressure at presentation 4
  • Unknown trigger 4
  • Drug trigger in children 4
  • Cardiovascular comorbidity or poorly controlled asthma 4
  • Adolescents/young adults with peanut or tree-nut allergy 4

Biphasic Reaction Risk

• Biphasic reactions occur in 1–20% of cases, typically around 11 hours after the initial reaction but can appear up to 72 hours later. 2, 4

• A prospective Australian study found delayed deterioration in 17% of ED anaphylaxis cases, with 53% requiring epinephrine and 69% of these occurring within 4 hours. 1

• Delayed epinephrine administration or inadequate initial dosing are risk factors for delayed deterioration. 1

Tryptase Sampling

• First sample: 1 hour after reaction onset 1, 4

• Second sample: 2–4 hours after onset 1, 4

• Baseline sample: At least 24 hours post-reaction for comparison 1, 4

Discharge Planning

Mandatory Discharge Requirements

• Prescribe two 0.3 mg epinephrine autoinjectors (or 0.15 mg for children 10–25 kg) with hands-on training in proper use. 2, 4

• Provide a written, personalized anaphylaxis emergency action plan that outlines:

  • Symptom recognition
  • Trigger avoidance
  • Clear instructions for epinephrine use
  • When to call 911 2, 4

• Education about biphasic reaction risk with clear instructions to return immediately if symptoms recur. 4

• Plan for monitoring autoinjector expiration dates—epinephrine degrades over time, reducing efficacy. 4

• Referral to allergist-immunologist for follow-up within 1–2 weeks to identify triggers and assess ongoing risk. 2, 4

Critical Safety Points and Common Pitfalls

Absolute Priorities

• There are no absolute contraindications to epinephrine in anaphylaxis—even in elderly patients with cardiovascular disease, the risk of death from untreated anaphylaxis far exceeds any epinephrine-related risk. 1, 2, 4

• Delayed epinephrine administration is directly linked to anaphylaxis fatalities—inject epinephrine first, then summon help. 1, 2, 4

Pitfalls to Avoid

• Never delay epinephrine while establishing IV access—IM injection achieves therapeutic levels faster than waiting for IV placement. 2, 4

• Do not rely on antihistamines or corticosteroids to treat life-threatening components (airway obstruction, cardiovascular collapse). 2, 4

• Avoid subcutaneous administration—it is too slow and should never be used. 2, 3

• Do not use the deltoid muscle for initial treatment—the anterolateral thigh provides superior absorption. 3

• Never discharge based solely on symptom resolution—biphasic reactions may develop many hours later. 4

• Do not use mandatory fixed observation periods for all patients—individualize based on risk factors, but err on the side of longer observation for high-risk features. 4, 5