What is the role of H1 (histamine 1) blockers and H2 (histamine 2) blockers in the treatment of anaphylaxis?

Role of H1 and H2 Blockers in Anaphylaxis Treatment

H1 and H2 antihistamines should only be used as adjunctive therapy in anaphylaxis after epinephrine administration, as they address only cutaneous manifestations and have limited evidence supporting their efficacy in treating life-threatening symptoms. 1

Primary Treatment of Anaphylaxis

• Epinephrine is the first-line therapy for anaphylaxis and should never be delayed or replaced by antihistamines 1, 2
• Intramuscular epinephrine (0.01 mg/kg of 1:1000 concentration, maximum 0.5 mg) should be administered into the vastus lateralis for optimal absorption 1
• Delay in administering epinephrine is associated with anaphylaxis fatalities and increased risk of biphasic reactions 1

Evidence for H1 Antihistamines in Anaphylaxis

• H1 antihistamines are commonly administered in anaphylaxis but there is only indirect evidence supporting this practice 1, 3
• H1 antihistamines address only cutaneous manifestations of anaphylaxis (itching, urticaria, flushing), none of which are life-threatening 1, 4
• Key limitations of H1 antihistamines in anaphylaxis include:
  • Slow onset of action (30 minutes to start working, 60-120 minutes to reach peak plasma levels) 1, 4
  • Lack of vasoconstrictive, bronchodilatory, ionotropic, and mast cell stabilization properties 1, 2
  • Cannot reverse cardiovascular and respiratory effects of anaphylaxis 4, 2

Evidence for H2 Antihistamines in Anaphylaxis

• A systematic review found no high-quality evidence supporting the use of H2 antihistamines in anaphylaxis 1, 5
• H2 receptors are primarily found in the gastrointestinal tract with limited distribution in vascular smooth muscle cells 1, 4
• H2 antihistamines play a minor role in the pathophysiology of anaphylaxis 4

FDA-Approved Use of Antihistamines in Anaphylaxis

• Diphenhydramine (H1 blocker) is FDA-approved "for amelioration of allergic reactions to blood or plasma, in anaphylaxis as an adjunct to epinephrine and other standard measures after the acute symptoms have been controlled" 6

Clinical Application of Antihistamines in Anaphylaxis Management

• If antihistamines are used, they should only be administered after epinephrine in patients with anaphylaxis 1, 2
• For oral and IV dosing, first-generation H1 antihistamines such as diphenhydramine 25-50 mg are commonly used 1
• Some clinicians use H1 and H2 antihistamines concurrently, but rigorous studies supporting this approach in anaphylaxis are lacking 1, 7
• One study showed improved resolution of urticaria when combining H1 and H2 antagonists in acute allergic syndromes, but this was not specifically for anaphylaxis 8

Common Pitfalls in Anaphylaxis Management

• Using antihistamines as first-line treatment instead of epinephrine is a dangerous practice that can lead to delayed treatment of life-threatening symptoms 1, 2
• Relying on antihistamines alone to treat anaphylaxis is inadequate as they cannot address cardiovascular collapse or respiratory distress 1, 2
• Sedation from first-generation H1 antihistamines may contribute to decreased awareness of anaphylaxis symptoms 1

Conclusion

When treating anaphylaxis, always remember the treatment algorithm:

1. Administer epinephrine immediately as first-line therapy
2. Consider antihistamines (H1 and possibly H2) only as adjunctive therapy for cutaneous symptoms
3. Recognize that antihistamines have limited evidence supporting their use and cannot replace epinephrine in treating life-threatening manifestations of anaphylaxis