What is the appropriate dose of diphenhydramine (Benadryl) intravenous (IV) for a patient with a bee sting experiencing an allergic reaction?

Diphenhydramine IV Dosing for Bee Sting Allergic Reactions

For a patient with a bee sting experiencing an allergic reaction, diphenhydramine IV should be dosed at 1-2 mg/kg (maximum 50 mg) administered at a rate not exceeding 25 mg/min, but only as adjunctive therapy after intramuscular epinephrine has been given first. 1, 2

Critical First-Line Treatment: Epinephrine, Not Diphenhydramine

Epinephrine is the only first-line treatment for anaphylaxis from bee stings—diphenhydramine is never a substitute and should only be considered after epinephrine administration. 1, 3

• Intramuscular epinephrine 0.01 mg/kg (maximum 0.3 mg in children, 0.3-0.5 mg in adults) into the anterolateral thigh must be given immediately for any systemic reaction beyond isolated mild skin symptoms 1, 3
• Fatal bee sting reactions are consistently associated with delayed or absent epinephrine administration 1
• Antihistamines and corticosteroids cannot substitute for epinephrine in life-threatening reactions 1

When to Use Diphenhydramine IV

For Mild Cutaneous-Only Reactions

• If the patient has only flushing, urticaria, or mild angioedema without respiratory, cardiovascular, or gastrointestinal symptoms, H1 antihistamines like diphenhydramine can be used as primary treatment 1
• However, close observation is mandatory because progression to anaphylaxis can occur, requiring immediate epinephrine 1

As Adjunctive Therapy After Epinephrine

• Once epinephrine has been administered for anaphylaxis, diphenhydramine IV can be given as adjunctive treatment 1
• The FDA-approved dosing is: 2
  • Pediatric patients: 5 mg/kg/24 hours or 150 mg/m²/24 hours, divided into four doses, maximum daily dose 300 mg
  • Adults: 10-50 mg IV at a rate not exceeding 25 mg/min, up to 100 mg if required, maximum daily dose 400 mg

Practical Dosing Algorithm

For children with systemic reactions (after epinephrine): 1, 2

• Calculate 1-2 mg/kg per dose
• Maximum single dose: 50 mg
• Administer IV at ≤25 mg/min
• Can repeat every 6 hours for 2-3 days as part of post-anaphylaxis management

For adults with systemic reactions (after epinephrine): 1, 2

• Give 25-50 mg IV at ≤25 mg/min
• Maximum single dose: 50 mg (or up to 100 mg if severe)
• Can repeat every 6 hours for 2-3 days

Common Pitfalls to Avoid

Never delay epinephrine to give antihistamines first. This is the most critical error in anaphylaxis management and is associated with fatal outcomes 1, 4, 5

• In one retrospective study of bee and wasp anaphylaxis, only 54% of moderate-to-severe cases received epinephrine, while 88-91% received IV glucocorticoids and antihistamines—this represents dangerous undertreatment 4
• Even in severe anaphylaxis (grade 5), epinephrine was administered in only 80% of cases, demonstrating widespread failure to follow guidelines 4

Recognize that diphenhydramine alone is insufficient for anything beyond isolated mild skin symptoms. 1

Post-Treatment Considerations

After initial stabilization with epinephrine and adjunctive diphenhydramine: 1

• Observe for 4-6 hours minimum for biphasic reactions (longer if severe initial reaction)
• Continue diphenhydramine every 6 hours for 2-3 days post-discharge
• Add H2 antihistamine (ranitidine) twice daily for 2-3 days
• Add corticosteroid (prednisone) daily for 2-3 days
• Prescribe epinephrine auto-injector with training before discharge
• Refer to allergist for venom-specific IgE testing and consideration of venom immunotherapy