What are the recommended acute and long‑term treatment options for a patient with severe allergic reactions, including anaphylaxis?

Treatment of Severe Allergies and Anaphylaxis

Intramuscular epinephrine 0.01 mg/kg (maximum 0.5 mg in adults, 0.3 mg in children) injected into the anterolateral thigh is the only first-line treatment for anaphylaxis and must be administered immediately at the first sign of a severe allergic reaction—there are no absolute contraindications, and all other medications are secondary. 1, 2, 3

Acute Management: First-Line Treatment

Immediate Epinephrine Administration

• Administer intramuscular epinephrine immediately into the vastus lateralis muscle (anterolateral thigh) at the first sign of anaphylaxis—this is the only medication proven to prevent death from anaphylaxis. 1, 2
• Dosing: 0.01 mg/kg of 1:1000 solution (1 mg/mL), with maximum doses of 0.5 mg in adults and 0.3 mg in children/teenagers. 1, 2
• Repeat dosing every 5-15 minutes if symptoms persist or worsen—do not hesitate to give multiple doses. 1, 2
• Critical principle: When in doubt about whether a reaction is anaphylaxis, err on the side of administering epinephrine—delaying administration increases morbidity and mortality. 1, 4

Supportive Measures (After Epinephrine)

• Position the patient supine with lower extremities elevated if cardiovascular symptoms predominate; avoid this position if respiratory distress worsens. 1, 2
• Administer supplemental oxygen at 6-8 L/min for patients with respiratory distress or those requiring additional epinephrine doses. 1, 2
• Establish IV access immediately and give rapid fluid bolus: Normal saline 1-2 L at 5-10 mL/kg in the first 5 minutes for adults, then 20 mL/kg boluses for persistent hypotension. 1, 2
• For bronchospasm: Give inhaled beta-2 agonists (albuterol 4-8 puffs via MDI in children, 8 puffs in adults, or nebulized solution) only after epinephrine administration. 1, 2

Adjunctive Medications (Never Before Epinephrine)

Secondary Treatments

• H1 antihistamines (diphenhydramine 1-2 mg/kg IV or oral, maximum 50 mg) may provide symptomatic relief for urticaria and pruritus but should never delay or replace epinephrine. 1, 2
• H2 antihistamines (ranitidine 50 mg IV) can be added as adjunctive therapy. 2
• Corticosteroids (methylprednisolone 1-2 mg/kg IV every 6 hours) are frequently used but have no proven role in acute treatment due to slow onset of action and do not reliably prevent biphasic reactions. 1, 2

Critical caveat: The 2020 practice parameter update specifically recommends against using antihistamines or glucocorticoids to prevent biphasic anaphylaxis, though they may be considered for secondary symptom management. 1

Refractory Anaphylaxis Management

For Persistent Hypotension Despite IM Epinephrine

• IV epinephrine infusion: 1:10,000 concentration administered slowly, or continuous infusion at 4.0 μg/mL concentration starting at 1-4 μg/min, increasing to maximum 10 μg/min if needed. 2
• Vasopressors: Dopamine 400 mg in 500 mL at 2-20 μg/kg/min OR vasopressin 0.01-0.04 U/min for persistent shock. 2
• Aggressive volume resuscitation with crystalloids or colloids is essential for refractory cases. 1, 2

Observation Period and Biphasic Reactions

Duration of Monitoring

• Standard cases: Minimum 4-6 hours observation after complete symptom resolution. 1, 2
• Severe anaphylaxis or multiple epinephrine doses: At least 6 hours observation, potentially up to 24 hours for highest-risk patients. 1, 2
• Biphasic reactions occur in 1-20% of cases (typically around 8 hours but can occur up to 72 hours later) and cannot be reliably prevented by antihistamines or corticosteroids. 1, 2

Risk Factors for Biphasic Reactions

• Severe initial presentation requiring multiple epinephrine doses 1
• Wide pulse pressure 1
• Unknown anaphylaxis trigger 1
• Cutaneous signs and symptoms 1
• Drug trigger in children 1
• Cardiovascular comorbidity or lack of access to emergency care 1

Long-Term Management and Prevention

Mandatory Discharge Requirements

• Prescribe two epinephrine autoinjectors for all patients—0.15 mg for children 10-25 kg, 0.3 mg for patients ≥25-30 kg. 1, 2
• Provide written anaphylaxis emergency action plan with clear instructions on when and how to use epinephrine. 1, 2
• Train on proper autoinjector technique before discharge—many patients fail to use autoinjectors even during severe reactions due to lack of familiarity. 1
• Refer to allergist-immunologist for trigger identification, comprehensive evaluation, and consideration of allergen immunotherapy when appropriate. 1, 2

High-Risk Populations Requiring Epinephrine Prescription

• Previous anaphylaxis or systemic allergic reaction 1, 2
• Food allergy combined with asthma (especially poorly controlled) 1, 2
• Known allergy to peanuts, tree nuts, fish, or crustacean shellfish 1, 2
• Idiopathic anaphylaxis 1
• Consider for all patients with IgE-mediated food allergies 2

Allergen-Specific Immunotherapy

• Venom immunotherapy is highly effective for patients with Hymenoptera (insect sting) anaphylaxis and should be considered for long-term prevention. 1
• Food immunotherapy protocols exist but require specialized allergist supervision. 1
• Immunotherapy has specific premedication protocols with antihistamines and/or glucocorticoids for rush protocols, though evidence for routine premedication in standard protocols is limited. 1

Common Pitfalls to Avoid

• Never delay epinephrine to administer antihistamines or corticosteroids first—this is the most common and dangerous error. 1
• Do not rely on oral antihistamines for initial treatment—they take 30-40 minutes to work, during which life-threatening symptoms can develop. 1
• Avoid subcutaneous epinephrine—intramuscular injection into the thigh provides faster and more reliable absorption than subcutaneous or deltoid injection. 1
• Do not discharge patients too early—even mild initial presentations can progress to biphasic reactions hours later. 1
• Ensure patients actually carry their autoinjectors—studies show many prescribed patients fail to carry them consistently, leading to preventable deaths. 1