What is the immediate treatment for a patient of any age with a biphasic anaphylaxis reaction?

Immediate Treatment for Biphasic Anaphylaxis

Treat biphasic anaphylaxis identically to the initial anaphylaxis episode: administer intramuscular epinephrine immediately as first-line therapy, followed by supportive care—do not use glucocorticoids or antihistamines as primary treatment. 1

First-Line Treatment: Epinephrine

Epinephrine is the only first-line pharmacotherapy for both uniphasic and biphasic anaphylaxis. 1

• Administer 0.3-0.5 mg intramuscular epinephrine (1:1000 concentration) for adults and adolescents >50 kg into the vastus lateralis (mid-outer thigh). 1, 2
• For prepubertal children, give 0.01 mg/kg intramuscular epinephrine (maximum 0.3 mg) into the anterolateral thigh. 1, 2
• Repeat epinephrine every 5-15 minutes if symptoms persist or recur, as approximately 10-20% of patients require multiple doses. 2, 3
• Do not delay epinephrine administration, as delays are associated with higher morbidity, mortality, and increased risk of further biphasic reactions. 1

Critical Patient Positioning and Supportive Care

• Position the patient supine with lower extremities elevated unless respiratory distress or vomiting is present. 2, 3
• Never allow the patient to stand, walk, or run, as this can precipitate cardiovascular collapse. 2
• Commence fluid resuscitation immediately with normal saline (5-10 mL/kg in first 5 minutes for adults; up to 30 mL/kg in first hour for children) if hypotension is present. 1, 3
• Provide supplemental oxygen at 6-8 L/min for patients with respiratory symptoms. 2, 3

Adjunctive Therapies (Only AFTER Epinephrine)

• H1-antihistamines (diphenhydramine 25-50 mg IV/IM) may be administered but only address cutaneous manifestations and are not life-saving. 1, 3
• H2-antihistamines (ranitidine 50 mg IV or famotidine 20 mg IV) can be added, though high-quality evidence for efficacy is lacking. 1, 3
• Albuterol nebulizer may be used for persistent bronchospasm unresponsive to epinephrine. 3

Glucocorticoids: NOT Recommended for Biphasic Prevention

Recent consensus guidelines explicitly recommend AGAINST administering glucocorticoids to prevent biphasic anaphylaxis. 1

• Multiple studies and systematic reviews have not demonstrated clear evidence that glucocorticoids prevent biphasic anaphylaxis. 1
• Glucocorticoids have no role in treating acute anaphylaxis given their slow onset of action (hours). 1
• The 2020 Joint Task Force on Practice Parameters found no clear evidence to support glucocorticoids or antihistamines preventing biphasic reactions. 1

Observation and Monitoring Requirements

• Transfer all patients to the emergency department for extended observation, even if symptoms resolve completely. 1
• Observe for minimum 4-6 hours after complete symptom resolution, with extended observation up to 6 hours or longer (including hospital admission) for severe anaphylaxis or patients requiring multiple epinephrine doses. 1, 2, 3
• Biphasic anaphylaxis can occur up to 72 hours later (mean 11 hours) after initial symptom resolution. 1
• Patients requiring >1 dose of epinephrine have significantly higher risk of biphasic reaction (odds ratio = 4.82). 1

Special Populations: Patients on Beta-Blockers

• For patients on beta-blockers who are refractory to epinephrine, administer glucagon 1-5 mg IV over 5 minutes (20-30 mcg/kg for children, maximum 1 mg), followed by infusion at 5-15 mcg/min. 3
• Consider intravenous epinephrine infusion (1:10,000 concentration) for protracted anaphylaxis unresponsive to intramuscular dosing. 1

Discharge Planning After Biphasic Reaction

• Prescribe two epinephrine auto-injectors with hands-on training on proper use. 2, 3
• Provide a written anaphylaxis emergency action plan with education on trigger avoidance, signs/symptoms, and biphasic reaction risk. 1, 2
• Refer to an allergist for evaluation within 1-2 weeks. 2
• Educate patients that self-injectable epinephrine should be available at discharge for prompt treatment if biphasic reaction occurs. 1

Common Pitfalls to Avoid

• Do not substitute antihistamines or glucocorticoids for epinephrine—they are not effective for acute anaphylaxis treatment. 1
• Do not discharge patients prematurely—biphasic reactions can occur many hours after initial resolution. 1, 2
• Do not rely on glucocorticoids to prevent biphasic reactions—the evidence does not support this practice despite historical use. 1
• Do not delay repeat epinephrine if symptoms persist or progress—early epinephrine administration reduces risk of subsequent biphasic reactions. 1