What are the recommended medications, doses, and routes for managing anaphylaxis in adults and children, including epinephrine, antihistamines, corticosteroids, bronchodilators, and supportive care?

Anaphylaxis Medication Dosing and Routes

Intramuscular epinephrine 0.3–0.5 mg (1:1000) in the mid-anterolateral thigh is the only first-line treatment for anaphylaxis in adults, with 0.01 mg/kg (maximum 0.3 mg) for children, and must be administered immediately—all other medications are adjunctive and must never delay or replace epinephrine. 1, 2

Epinephrine: First-Line Treatment

Dosing by Weight

• Adults and adolescents ≥50 kg: 0.3–0.5 mg of 1:1000 (1 mg/mL) epinephrine intramuscularly 1, 2
• Children <50 kg: 0.01 mg/kg intramuscularly, maximum 0.3 mg 1, 2
• Autoinjector dosing:
  • 0.1 mg for infants >7.5 kg (where available; otherwise 0.15 mg is acceptable) 2, 3
  • 0.15 mg for children 10–25 kg 1, 2
  • 0.3 mg for patients ≥25 kg 1, 2

Route and Technique

• Injection site: Mid-anterolateral thigh (vastus lateralis muscle)—this is the only acceptable first-line location 2, 4
• Pharmacokinetic rationale: Intramuscular thigh injection achieves peak plasma concentration in 8±2 minutes versus 34±14 minutes with subcutaneous deltoid injection 1, 2, 4
• Never use subcutaneous route—delayed absorption significantly compromises efficacy 4
• Can inject through clothing if necessary—do not delay for clothing removal 2

Repeat Dosing Protocol

• Repeat every 5–15 minutes if symptoms persist or recur 1, 2
• 10–28% of patients require a second dose, and some require more 2, 4
• The 5-minute interval can be shortened in severe clinical situations 2
• Continue dosing based on clinical response rather than an arbitrary maximum number 2

Critical Safety Points

• No absolute contraindications exist for epinephrine in anaphylaxis—even in elderly patients with cardiovascular disease, the mortality risk from untreated anaphylaxis far exceeds any epinephrine-related risk 2, 3, 5
• Delayed epinephrine is directly linked to anaphylaxis fatalities—inject first, then call for help 2, 6, 7

Immediate Supportive Measures (Concurrent with Epinephrine)

Patient Positioning

• Place supine with legs elevated unless respiratory distress or vomiting precludes this position 1, 2, 3
• Never allow patient to stand or walk—upright positioning increases mortality risk 2
• In pregnant patients, perform left uterine displacement to avoid aortocaval compression 3

Oxygen and Airway

• Administer supplemental oxygen at 6–8 L/min for any patient with respiratory symptoms or who requires multiple epinephrine doses 1, 2
• Prepare for emergency cricothyroidotomy or tracheostomy if severe laryngeal edema prevents intubation 2

Fluid Resuscitation

• Adults: Normal saline bolus 1,000–2,000 mL (5–10 mL/kg) within first 5 minutes 1, 2, 3
• Children: Up to 30 mL/kg in the first hour 1, 2
• Repeat boluses as needed—some patients require 20–30 mL/kg total 2, 3
• Fluid resuscitation is imperative because anaphylaxis causes massive vasodilation and capillary leak 3

Adjunctive Medications (Second-Line Only—After Epinephrine)

H1 Antihistamines

• Diphenhydramine 25–50 mg IV/IM (or 1–2 mg/kg in children, maximum 50 mg) 1, 2, 3
• Alternative: Cetirizine 10 mg orally (less sedating) 2
• Indication: Urticaria and pruritus only—does NOT relieve airway obstruction, bronchospasm, GI symptoms, or shock 2, 4
• Must never be given before or in place of epinephrine 1, 4

H2 Antihistamines

• Ranitidine 50 mg IV or famotidine 20 mg IV in adults (1–2 mg/kg in children) 1, 2, 3
• May be added to H1 blocker, but evidence of benefit is minimal 2, 3

Bronchodilators

• Albuterol (salbutamol) nebulized 2.5–5 mg in 3 mL saline or MDI (4–8 puffs in children, 8 puffs in adults) 1, 2
• Indication: Persistent bronchospasm after epinephrine 1
• Does NOT treat airway edema or cardiovascular collapse 2

Corticosteroids

• NOT recommended for acute anaphylaxis treatment—slow onset of action (4–6 hours) and no proven benefit in preventing biphasic reactions 1, 2, 3
• If used empirically: Methylprednisolone 1–2 mg/kg IV every 6 hours or hydrocortisone 200 mg IV 1, 2
• Must never be given before or in place of epinephrine 1

Management of Refractory Anaphylaxis

Intravenous Epinephrine (Hospital Setting Only)

• Indication: Failure to respond after 2–3 intramuscular doses (approximately 10 minutes of treatment) 2
• Bolus dosing:
  • Adults: 50–100 µg IV (0.5–1 mL of 1:10,000 concentration) 2, 3
  • Children: 1 µg/kg IV 2
  • Repeat every 2–5 minutes if inadequate response 2
• Continuous infusion: 0.05–0.1 µg/kg/min (≈1–4 µg/min in adults, maximum 10 µg/min) 1, 2, 3
• Preparation: Add 1 mg (1 mL) of 1:1000 epinephrine to 250 mL D5W to yield 4 µg/mL concentration 2
• Critical safety: Use ONLY 1:10,000 (0.1 mg/mL) concentration for IV administration—using 1:1000 can cause fatal arrhythmias 2, 4
• Requires continuous cardiac monitoring 2

Alternative Vasopressors

• Vasopressin: 1–2 IU bolus, then infusion at 2 IU/hour 2, 3
• Norepinephrine: Infusion at 0.05–0.5 µg/kg/min 2, 3
• Phenylephrine or metaraminol may also be used for persistent hypotension 3

Special Considerations

• Patients on β-blockers: Glucagon 1–5 mg IV over 5 minutes (20–30 µg/kg in children, maximum 1 mg), followed by infusion of 5–15 µg/min 1, 2
• Bradycardia: Atropine IV 1, 2

Observation and Biphasic Reaction Risk

Minimum Observation Period

• 4–6 hours after complete symptom resolution in a facility capable of managing anaphylaxis 1, 2, 3
• Extended observation (≥6 hours) or admission required for:
  • Patients who received >1 epinephrine dose (strongest predictor) 1, 2
  • Severe initial presentation (hypotension, respiratory compromise) 1, 2
  • Wide pulse pressure 1, 2
  • Unknown trigger 1, 2
  • Drug trigger in children 1
  • Coexisting asthma, especially poorly controlled 2
  • Cardiovascular comorbidity 2

Biphasic Reaction Facts

• Occurs in 1–20% of cases, typically around 8 hours but can appear up to 72 hours later 2, 3
• In one prospective study, 17% experienced delayed deterioration; 53% of those required epinephrine, and 69% of repeat doses occurred within 4 hours 2
• Antihistamines and corticosteroids do NOT reliably prevent biphasic reactions 1, 2

Discharge Requirements (All Patients)

• Two epinephrine autoinjectors (appropriate dose for weight) with hands-on training 2, 3, 4
• Written anaphylaxis emergency action plan detailing symptoms, triggers, and epinephrine use instructions 2, 4
• Education on:
  • Trigger avoidance 1
  • Early recognition of anaphylaxis signs 1
  • Proper autoinjector technique 1
  • Monitoring device expiration dates 2, 4
  • Biphasic reaction risk and need to seek emergency care after epinephrine use 2, 4
• Referral to allergist-immunologist for follow-up within 1–2 weeks 1, 2
• Medical identification jewelry or wallet card 1

Common Pitfalls to Avoid

• Never delay intramuscular epinephrine while establishing IV access—IM achieves therapeutic levels faster 2, 4
• Never substitute antihistamines or corticosteroids for epinephrine—they do not treat life-threatening components 2, 4
• Never discharge based solely on symptom resolution—biphasic reactions can develop hours later 2
• Never use 1:1000 concentration for IV administration—only 1:10,000 is safe 2, 4
• Do not assume absence of skin findings rules out anaphylaxis—nearly 30% lack cutaneous manifestations 2