Lit of the Week — Antihistamines in Acute Allergic Reaction

Lin RY, Curry A, Pesola GR, Knight RJ, Lee HS, Bakalchuk L, Tenenbaum C, Westfal RE. Improved outcomes in patients with acute allergic syndromes who are treated with combined H1 and H2 antagonists. Ann Emerg Med. 2000 Nov;36(5):462-8. PubMed PMID: 11054200.

Clinical question / background:

• Does combined H1 and H2 blockade result in improved outcomes in patients treated for acute allergic syndromes compared with treatment with H1 blockers alone?

Design:

• Randomized, double-blind, placebo-controlled trial
• 91 patients, 1 urban academic center emergency department
• Inclusion: Adults (> 18 y/o) presenting after exposure to ingested food, exposure to drug, or contact with latex with acute urticaria, acute angioedema, acute unexplained stridor, and acute pruritic rash for < 12 hours
• Exclusion: Pregnant patients
• Supplemental medications such as O2, IVF, Epinephrine, Steroids, Bronchodilators, Additional antihistamine doses given at discretion of physicians
• Primary outcome: resolution of urticaria and angioedema at 2 hours
• Secondary outcomes: changes in vital signs, final disposition

Intervention:

• Diphenhydramine 50 mg IV x1 + Ranitidine 50 mg IV x 1

Control:

• Diphenhydramine 50 mg IV x 1 + saline solution

Results:

• Significant difference in patients without urticaria at 2 hours between Ranitidine group (91.7%) and placebo group (73.8%), p=0.02
• Number of areas involved with urticaria at 2 hours significantly less in ranitidine group
• Significantly higher proportion of patients without angioedema and urticaria at 2 hours in ranitidine group (70.5% vs placebo (46.5%), p=0.02
• OR of ranitidine treatment 2.80

Take-home:

• Benefit of adding H2 blockers to H1 blockers in treatment of cutaneous manifestations of allergic reactions

Strengths:

• Well-designed, double-blinded

Weaknesses / Critiques

• Small sample size, 91 total patients
• Potential confounders of steroid treatment, bronchodilators, additional antihistamine doses in placebo group
• Parenteral administration so no data on PO
• Authors purport epinephrine administration was not a confounder based on their analysis
• Not enough data to extrapolate to treatment of anaphylaxis

Follow-up / Real World Application

• Allergic reaction – usually skin manifestations of urticaria / erythema
  • H1/H2 blockers +/- steroids (Methylprednisolone 125 mg IV/IM or Prednisone 60 mg PO)
• Angioedema — Localized subcutaneous (or submucosal) swelling
  • ALL patients – assess for airway compromise
  • Hereditary (C1 esterase deficiency)
    • RX FFP or if available C1 esterase inhibitors (Berinert 20u/kg IV), kallikrein/bradykinin inhibitors (ecallantide30mg SQ), or bradykinin receptor antagonist (icantibant 30mg SQ)
  • ACE-inhibitor induced or Allergic / Idiopathic
    • D/C ACE-I if applicable
    • Methylprednisolone 125 mg IV/IM
    • H1/H2 blockers IV
    • If accompanied by anaphylaxis, Epi 0.3-0.5 mg IM q 15-20 PRN
  • Anaphylaxis
    • Criterion 1 – acute onset of illness involving skin, mucosa (or both) AND
      • Respiratory compromise
      • Hypotension (or symptom such as syncope)
    • Criterion 2 – exposure to potential allergen + 2 or more of following
      • Involvement of skin-mucosal tissue
      • Respiratory compromise
      • Hypotension (or symptom such as syncope)
      • Persistent GI sxs (Nausea/vomiting, diarrhea, abd pain)
    • Criterion 3 – exposure of known allergen + hypotension
    • RX –
      • Epi 1:1000 0.3-0.5 mg IM q5-15 PRN
      • If no response, start epi drip: 1:10,000 2-10 mcg/min IV gtt
      • Peds: Epi 1:1000 0.01 mg/kg (max 0.5 mg)
        • 05-1 mcg/kg/min gtt if infusion necessary
      • Airway management
      • Albuterol, Steroids, H1/H2 blockers