What is the first‑line treatment for a moderate to severe acute allergic reaction (anaphylaxis) presenting with urticaria, angio‑edema, respiratory distress, hypotension, or gastrointestinal symptoms?

First-Line Treatment for Acute Allergic Reaction (Anaphylaxis)

Intramuscular epinephrine injected into the mid-anterolateral thigh is the only first-line treatment for moderate to severe anaphylaxis and must be administered immediately—all other interventions are adjunctive and must never delay epinephrine. 1, 2, 3

Immediate Epinephrine Administration

Dosing and Route

• Adults and adolescents ≥30 kg: Administer 0.3–0.5 mg of 1:1000 (1 mg/mL) epinephrine intramuscularly. 1, 2
• Children <30 kg: Administer 0.01 mg/kg intramuscularly (maximum 0.3 mg). 1, 2
• Injection site: The vastus lateralis (mid-outer thigh) achieves peak plasma concentrations in 8±2 minutes, compared with 34±14 minutes for subcutaneous administration. 1, 2
• Repeat dosing: If symptoms persist or recur, repeat epinephrine every 5–15 minutes; 10–20% of patients require more than one dose. 1, 2, 3

Critical Safety Point

Delayed epinephrine administration is directly associated with anaphylaxis fatalities. 2, 4 There are no absolute contraindications to epinephrine in anaphylaxis—even in elderly patients with cardiovascular disease, the risk of death from untreated anaphylaxis outweighs any theoretical cardiac concerns. 1, 2

Concurrent Supportive Measures (Do Not Delay Epinephrine)

Immediate Actions

• Activate emergency medical services (call 911 or summon resuscitation team) as soon as anaphylaxis is recognized. 1, 2
• Remove the offending allergen immediately to stop ongoing exposure. 1, 2
• Position the patient supine with legs elevated (unless respiratory distress or vomiting precludes this); in pregnant patients, perform left uterine displacement to avoid aortocaval compression. 1, 2

Airway and Breathing

• Administer 100% oxygen at 6–8 L/min for any patient with respiratory symptoms or who has required multiple epinephrine doses. 1, 2
• Secure the airway promptly; prepare for intubation if necessary and be ready for emergency cricothyrotomy in cases of severe laryngeal edema. 1, 2

Fluid Resuscitation

• Establish intravenous access immediately and begin aggressive crystalloid infusion (normal saline or lactated Ringer's). 1, 2
• Adults: Administer 5–10 mL/kg (approximately 1–2 L) within the first 5 minutes; up to 20–30 mL/kg may be required for severe vasodilation and capillary leak. 1, 2
• Children: Give up to 30 mL/kg within the first hour. 1, 2

Adjunctive Pharmacologic Therapies (After Epinephrine)

Bronchodilators

• For persistent bronchospasm after epinephrine: Administer inhaled albuterol 2.5–5 mg nebulized in 3 mL saline or via metered-dose inhaler. 1, 2
• Important caveat: Albuterol does not relieve airway edema (e.g., laryngeal edema) and should never be substituted for epinephrine. 1

Antihistamines (Second-Line Only)

• H1 antihistamine: Diphenhydramine 25–50 mg IV/IM (or 1–2 mg/kg in children) is indicated only for urticaria and itching—it does not relieve stridor, bronchospasm, gastrointestinal symptoms, or shock. 1, 2, 4
• Alternative H1: Cetirizine 10 mg orally (second-generation, less sedating) may be used. 1, 4
• H2 antihistamine: Ranitidine 50 mg IV or famotidine 20 mg IV may be added to H1 blockade, but evidence of clinical benefit is minimal. 1, 2, 4

Corticosteroids (Not Recommended for Acute Phase)

Corticosteroids have a slow onset of action (4–6 hours) and do not help in the acute treatment of anaphylaxis. 1, 3, 4 They do not prevent biphasic reactions and should never delay or replace epinephrine. 1, 3, 4 If administered empirically, use methylprednisolone 1–2 mg/kg/day IV every 6 hours or hydrocortisone 200 mg IV, recognizing the weak evidence base. 1, 2

Management of Refractory Anaphylaxis

When to Consider Refractory Anaphylaxis

Hypotension or bronchospasm persists despite ≥3 intramuscular epinephrine doses and adequate fluid resuscitation. 2

Intravenous Epinephrine (Monitored Setting Only)

• Use only 1:10,000 (0.1 mg/mL) concentration for IV administration—never use the 1:1000 concentration intended for intramuscular injection, as this can cause fatal arrhythmias. 1, 2
• Adults: 50–100 µg IV bolus (0.5–1 mL of 1:10,000), titrated to effect; repeat every 5–15 minutes as needed. 1, 2
• Children: 1 µg/kg IV bolus. 2
• Continuous infusion: 0.05–0.1 µg/kg/min (approximately 1–4 µg/min in adults, maximum 10 µg/min) with continuous cardiac monitoring. 1, 2

Special Populations

• Patients on β-blockers: May be refractory to epinephrine; administer glucagon 1–5 mg IV over 5 minutes (20–30 µg/kg in children, maximum 1 mg), followed by an infusion of 5–15 µg/min. 1, 2
• Persistent hypotension: Consider alternative vasopressors such as norepinephrine, vasopressin, phenylephrine, or dopamine. 1, 2
• Bradycardia: Treat with IV atropine. 1, 2

Observation and Monitoring

Minimum Observation Period

• All patients: Observe for a minimum of 4–6 hours after complete symptom resolution in a facility capable of managing anaphylaxis. 1, 2

Extended Observation or Admission Criteria

Extended observation (≥6 hours) or hospital admission is required for patients with any of the following high-risk features:

• Received >1 epinephrine dose (strongest predictor of biphasic reaction) 2
• Severe initial presentation (hypotension, respiratory compromise, cardiovascular instability) 2
• Wide pulse pressure at presentation 2
• Unknown anaphylaxis trigger 2
• Drug trigger in children 2
• Cardiovascular comorbidity 2
• Coexisting asthma, especially poorly controlled 2
• Adolescents/young adults with peanut or tree-nut allergy 2
• Refractory or protracted symptoms despite treatment 2

Biphasic Anaphylaxis Risk

Biphasic anaphylaxis—recurrence after appropriate initial treatment—occurs in 1–20% of cases, typically around 8 hours after the initial reaction but may appear up to 72 hours later. 1, 2 Predictors include severe initial presentation, multiple epinephrine doses, wide pulse pressure, unknown trigger, and prominent skin/mucosal signs. 1, 2

Discharge Planning

Mandatory Discharge Requirements

• Two epinephrine autoinjectors with hands-on training (0.15 mg for 10–25 kg; 0.3 mg for ≥25 kg). 2, 3
• Written anaphylaxis emergency action plan detailing common symptoms, clear epinephrine administration instructions, known triggers, and the need to seek emergency care after use. 2
• Education about biphasic reaction risk and clear instructions to return immediately if symptoms recur. 2
• Plan for monitoring autoinjector expiration dates. 2
• Referral to an allergist-immunologist for comprehensive evaluation within 1–2 weeks. 2

Critical Pitfalls to Avoid

• Do not delay intramuscular epinephrine while establishing IV access—IM injection achieves therapeutic levels more rapidly. 1, 2
• Do not rely on antihistamines or corticosteroids to treat airway obstruction or cardiovascular collapse—these agents only address cutaneous symptoms and have no effect on life-threatening manifestations. 1, 2, 4
• Do not discharge a patient solely based on symptom resolution—biphasic reactions can develop many hours later. 2
• Do not use 1:1000 epinephrine concentration for IV administration—only 1:10,000 is safe for intravenous use. 1, 2
• Recognize that bradycardia occurs in approximately 10% of anaphylactic episodes and does not exclude the diagnosis. 2
• Understand that the absence of cutaneous signs does not rule out anaphylaxis—nearly 30% of patients lack skin findings. 2