What is the recommended immediate management of anaphylaxis, including epinephrine dosing, patient positioning, oxygen therapy, fluid resuscitation, adjunct medications, observation period, and follow‑up?

Treatment of Anaphylaxis

Intramuscular epinephrine 0.3–0.5 mg (1:1000 concentration) injected into the mid-anterolateral thigh is the only first-line treatment for anaphylaxis and must be administered immediately upon recognition—all other interventions are adjunctive and should never delay epinephrine. 1, 2

Immediate First-Line Treatment: Epinephrine

• Dose for adults and children ≥30 kg: 0.3–0.5 mg of 1:1000 epinephrine (1 mg/mL) intramuscularly. 2, 3
• Dose for children <30 kg: 0.01 mg/kg intramuscularly (maximum 0.3 mg). 1, 2
• Injection site: Mid-anterolateral thigh (vastus lateralis) using a 90° angle—this achieves peak plasma concentrations in 8±2 minutes versus 34±14 minutes with subcutaneous administration. 2, 3
• Repeat dosing: Administer every 5–15 minutes as needed if symptoms persist or recur; approximately 10–20% of patients require more than one dose. 1, 2, 3
• Critical timing: Delayed epinephrine administration is directly associated with anaphylaxis fatalities—inject first, then call for help. 1, 2

Autoinjector Prescriptions for Discharge

• Prescribe two epinephrine autoinjectors at discharge: 0.15 mg for children 10–25 kg, 0.3 mg for individuals ≥25 kg, and 0.1 mg for infants where available (if unavailable, 0.15 mg is appropriate for infants >7.5 kg). 2

Concurrent Initial Actions (Do Not Delay Epinephrine)

• Call for help immediately: Activate emergency medical services (911) or summon a resuscitation team in the hospital setting. 1
• Remove the allergen: Eliminate any ongoing allergen exposure. 1
• Position the patient: Place supine with legs elevated unless respiratory distress or vomiting makes this intolerable; in pregnant women, perform left uterine displacement to avoid aortocaval compression. 1, 2
• Never allow the patient to stand or walk—sudden postural changes can precipitate cardiovascular collapse. 2

Supplemental Oxygen and Airway Management

• Administer 100% oxygen at 6–8 L/min for any patient with respiratory symptoms or who required multiple epinephrine doses. 1, 2
• Secure the airway early if laryngeal edema is present; be prepared for emergency cricothyroidotomy or tracheostomy if conventional intubation becomes impossible. 2

Aggressive Fluid Resuscitation

• Establish IV access immediately and administer isotonic crystalloid (normal saline or lactated Ringer's). 1, 2
• Adults: Give 5–10 mL/kg rapidly in the first 5 minutes (approximately 1–2 L total); up to 20–30 mL/kg may be required for severe vasodilation. 2
• Children: Administer up to 30 mL/kg within the first hour. 2
• Grade II reactions: Initial bolus of 0.5 L crystalloid. 2
• Grade III reactions: Initial bolus of 1 L crystalloid, repeated as needed based on clinical response. 2

Fluid resuscitation is imperative because anaphylaxis causes profound vasodilation and capillary leak, potentially reducing circulating blood volume by up to 37%. 2

Adjunctive Medications (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—does not relieve airway obstruction, bronchospasm, gastrointestinal symptoms, or shock. 2, 3
• Alternative: Cetirizine 10 mg orally (second-generation, less sedating). 2

H2 Antihistamines

• Ranitidine 50 mg IV in adults (approximately 1 mg/kg in children) or famotidine 20 mg IV, given with an H1 antihistamine; evidence of benefit is minimal. 2, 3

Bronchodilators

• Nebulized albuterol 2.5–5 mg in 3 mL saline for persistent bronchospasm after epinephrine—does not treat airway edema or cardiovascular collapse. 2

Corticosteroids

• Not recommended for acute anaphylaxis because they have a slow onset of action (4–6 hours) and no proven benefit in preventing biphasic reactions. 2
• If administered empirically, methylprednisolone 1–2 mg/kg/day IV every 6 hours or hydrocortisone 200 mg IV, recognizing the weak evidence base; discontinue within 2–3 days. 2, 3

Management of Refractory Anaphylaxis

IV Epinephrine (Only When IM Fails)

• Indication: Persistent hypotension or shock after adequate IM epinephrine and fluid resuscitation. 2, 3
• Bolus dosing: 50–100 µg (0.05–0.1 mg) of 1:10,000 epinephrine IV slowly; pediatric dose is 1 µg/kg. 2, 3
• Continuous infusion: 0.05–0.1 µg/kg/min (approximately 1–4 µg/min in adults, maximum 10 µg/min), titrated to hemodynamic response. 2, 3
• Critical safety: Use only the 1:10,000 concentration (0.1 mg/mL) for IV administration—the 1:1000 concentration intended for IM injection can cause fatal arrhythmias. 2, 3
• Mandatory monitoring: Continuous cardiac monitoring and frequent blood pressure checks are required during IV epinephrine therapy. 2, 3

Alternative Vasopressors

• For persistent hypotension despite epinephrine and fluids, consider norepinephrine, vasopressin, phenylephrine, or metaraminol titrated to restore blood pressure. 2

Special Considerations for Beta-Blocker Patients

• 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; be aware of possible vomiting. 2, 3

Extreme Cases

• Extracorporeal life support may be considered in refractory cases. 2

Observation and Monitoring

Minimum Observation Period

• All patients: Observe for a minimum of 4–6 hours in a facility equipped to manage anaphylaxis after complete symptom resolution. 2
• High-risk patients: Extended observation (up to 6 hours or longer) or ICU admission is required for those who:
  • Required more than one epinephrine dose (strongest predictor of biphasic reaction) 2
  • Had severe initial presentation (hypotension, respiratory compromise, cardiovascular instability) 2
  • Presented with wide pulse pressure 2
  • Have an unknown trigger 2
  • Are children with drug-triggered reactions 2
  • Have cardiovascular comorbidity or poorly controlled asthma 2
  • Are adolescents/young adults with peanut or tree-nut allergy 2

Biphasic Anaphylaxis Risk

• Biphasic reactions occur in 1–20% of cases, typically around 8 hours after the initial reaction but can appear up to 72 hours later. 2
• The number needed to monitor to detect one biphasic reaction is 13 (95% CI: 7–27) for patients who required multiple epinephrine doses. 2

Mast Cell Tryptase Sampling

• First sample: 1 hour after reaction onset. 2
• Second sample: 2–4 hours after onset. 2
• Baseline sample: At least 24 hours post-reaction for comparison. 2

Discharge Requirements (All Patients)

• Two epinephrine autoinjectors with hands-on training in proper use. 2
• Written, personalized anaphylaxis emergency action plan detailing symptoms, triggers, and epinephrine administration instructions. 2
• Education about biphasic reaction risk with clear instructions to return immediately if symptoms recur. 2
• Plan for monitoring autoinjector expiration dates because epinephrine degrades over time. 2
• Referral to an allergist for follow-up evaluation within 1–2 weeks. 2

Critical Pitfalls to Avoid

• Never delay IM epinephrine while establishing IV access—IM injection achieves therapeutic levels faster than waiting for IV placement. 2
• Do not rely on antihistamines or corticosteroids as first-line therapy—they do not prevent or reverse cardiovascular collapse or airway obstruction. 1, 2
• There are no absolute contraindications to epinephrine in anaphylaxis, even in elderly patients with cardiovascular disease or those taking beta-blockers—the risk of death from untreated anaphylaxis far outweighs any potential epinephrine-related risk. 2
• If anaphylaxis progresses to cardiac arrest, immediately switch to cardiac arrest dosing: 1 mg of 1:10,000 epinephrine IV/IO every 3–5 minutes; do not continue IM dosing. 3, 4
• Do not discharge patients solely on symptom resolution—biphasic reactions may develop many hours later. 2