What is the role of chlorphenamine in the treatment of anaphylaxis?

Chlorphenamine in Anaphylaxis Treatment

Chlorphenamine (and all H1 antihistamines) should only be used as adjunctive therapy AFTER epinephrine administration in anaphylaxis, never as first-line treatment or as a substitute for epinephrine. 1, 2

Primary Treatment Framework

Epinephrine is the only first-line medication for anaphylaxis and must be administered immediately at 0.01 mg/kg of 1:1000 concentration (maximum 0.5 mg in adults, 0.3 mg in children) intramuscularly into the vastus lateralis. 1, 2 Delayed epinephrine administration is directly associated with anaphylaxis fatalities and increased risk of biphasic reactions. 1

Limited Role of Chlorphenamine and H1 Antihistamines

H1 antihistamines like chlorphenamine address only cutaneous manifestations (itching, urticaria, flushing) which are not life-threatening symptoms of anaphylaxis. 1 These medications have critical limitations:

• Slow onset of action: Typically 30 minutes to start working and 60-120 minutes to reach peak plasma levels 1
• Lack essential pharmacologic properties: No vasoconstrictive, bronchodilatory, ionotropic, or mast cell stabilization effects 1
• Cannot address life-threatening symptoms: Inadequate for cardiovascular collapse or respiratory distress 1

Evidence Base

The strength of evidence for H1 antihistamines in anaphylaxis is limited to indirect evidence only. 1 A 2020 systematic review found very low certainty of evidence regarding antihistamines in anaphylaxis treatment, with no randomized controlled trials supporting their use in most settings. 3 Importantly, antihistamines do not prevent biphasic anaphylaxis (OR 0.71; 95% CI 0.47-1.06). 3

Appropriate Clinical Application

If chlorphenamine or other H1 antihistamines are used, they should only be administered AFTER epinephrine in patients with anaphylaxis. 1 The rationale is limited to symptomatic relief of urticaria and pruritus to improve patient comfort during anaphylaxis. 3, 1

First-generation H1 antihistamines such as diphenhydramine 25-50 mg (or equivalent doses of chlorphenamine) are commonly used for oral and IV dosing when adjunctive therapy is chosen. 1

Critical Pitfalls to Avoid

Using chlorphenamine or any antihistamine as first-line treatment instead of epinephrine is a dangerous practice that can lead to delayed treatment of life-threatening symptoms. 1 Additional concerns include:

• Sedation from first-generation H1 antihistamines contributes to decreased awareness of anaphylaxis symptoms 1
• Providers cannot allow patients to "prefer" an antihistamine over epinephrine for anaphylaxis treatment 3
• If antihistamines are used prior to epinephrine administration, they could lead to a delay in first-line treatment 3

Clinical Decision Algorithm

1. Recognize anaphylaxis based on clinical criteria 2
2. Administer epinephrine immediately - do not delay 1, 2
3. Call emergency services and position patient appropriately 2
4. Consider chlorphenamine/antihistamines only after epinephrine for symptomatic relief of cutaneous symptoms 1
5. Monitor and repeat epinephrine if symptoms persist (5-15 minutes) 2
6. Transport to emergency department regardless of response 2