What is the appropriate management for a patient experiencing a biphasic anaphylactic reaction, particularly one with a history of allergies or asthma?

Management of Biphasic Anaphylactic Reactions

Patients experiencing biphasic anaphylaxis require immediate intramuscular epinephrine (0.3-0.5 mg for adults, 0.01 mg/kg for children) into the vastus lateralis, repeated every 5-15 minutes as needed, followed by extended observation of 4-6 hours minimum or hospital admission for severe cases requiring multiple epinephrine doses. 1

Immediate Treatment Protocol

First-Line: Epinephrine Administration

• Administer intramuscular epinephrine immediately at 0.01 mg/kg of 1:1000 concentration (maximum 0.5 mg in adults, 0.3 mg in children) into the anterolateral thigh (vastus lateralis). 1, 2
• Repeat epinephrine every 5-15 minutes if symptoms persist or recur—approximately 10-20% of patients require multiple doses. 1
• Early epinephrine administration reduces the risk of subsequent biphasic reactions—delays are associated with increased mortality and higher biphasic reaction rates. 1

Critical Supportive Care

• Position the patient supine with legs elevated unless respiratory distress or vomiting is present (standing or walking can precipitate cardiovascular collapse). 1
• Commence immediate fluid resuscitation 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
• Provide supplemental oxygen at 6-8 L/min for patients with respiratory symptoms. 1
• Administer inhaled beta-2 agonists (albuterol nebulizer) for persistent bronchospasm following initial epinephrine treatment. 1

Adjunctive Medications (Only AFTER Epinephrine)

Antihistamines

• H1-antihistamines (diphenhydramine 25-50 mg IV/IM) may be administered but only address cutaneous manifestations and are not life-saving. 1
• H2-antihistamines (ranitidine 50 mg IV or famotidine 20 mg IV) can be added, though high-quality evidence for efficacy is lacking. 1
• Antihistamines should never delay or substitute for epinephrine administration. 1

Glucocorticoids: NOT Recommended for Biphasic Prevention

• Multiple guidelines explicitly recommend AGAINST administering glucocorticoids to prevent biphasic anaphylaxis—systematic reviews have not demonstrated clear evidence that glucocorticoids prevent biphasic reactions. 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 preventing biphasic reactions. 1

Risk Stratification for Biphasic Reactions

High-Risk Features Requiring Extended Observation

• Severe initial anaphylaxis requiring aggressive treatment. 1
• Requirement of more than one dose of epinephrine to treat initial symptoms (odds ratio = 4.82 for biphasic reaction). 1
• Wide pulse pressure, unknown anaphylaxis trigger, or drug trigger in children. 1
• History of asthma or allergies increases risk of severe reactions. 1, 3

Observation Requirements

• All patients should be transferred to the emergency department for extended observation, even if symptoms resolve completely. 1, 4
• Minimum observation period: 4-6 hours after complete symptom resolution for all patients. 1, 3
• Extended observation up to 6 hours or longer (including hospital admission) for patients with severe anaphylaxis or requiring multiple epinephrine doses. 1
• Biphasic anaphylaxis can occur up to 72 hours later (mean 11 hours) after initial symptom resolution. 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. 1
• Consider intravenous epinephrine infusion (1:10,000 concentration) for protracted anaphylaxis unresponsive to intramuscular dosing. 1

Patients with Asthma

• Patients with coexisting asthma are at higher risk for severe or fatal anaphylactic reactions. 3
• Ensure aggressive treatment with epinephrine and beta-2 agonists for bronchospasm. 1

Discharge Planning After Biphasic Reaction

• Prescribe two epinephrine auto-injectors with hands-on training on proper use. 1, 3, 5
• Provide a written anaphylaxis emergency action plan with education on trigger avoidance, signs/symptoms, and biphasic reaction risk. 1, 3
• Refer to an allergist for evaluation within 1-2 weeks. 1, 3
• Educate patients that self-injectable epinephrine should be available for prompt treatment if biphasic reaction occurs. 1, 3, 5

Critical Pitfalls to Avoid

• Never 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, 4
• 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
• Avoid intramuscular injection sites other than the vastus lateralis—this allows optimal absorption. 1, 2