Can diphenhydramine (antihistamine) be given to a patient with difficulty breathing?

Diphenhydramine Should NOT Be Given for Difficulty Breathing

Do not administer diphenhydramine as a primary treatment for difficulty breathing unless the respiratory distress is clearly due to anaphylaxis or an acute allergic reaction, and even then, it must never be used alone—epinephrine is the first-line treatment. 1

Critical Safety Concerns with Diphenhydramine in Respiratory Distress

Contraindications and Warnings in Lower Respiratory Disease

• The FDA explicitly warns to "use with caution in patients with lower respiratory disease including asthma" and notes that diphenhydramine should be used cautiously in patients with "a history of bronchial asthma." 2

• The FDA oral formulation specifically advises patients to "ask a doctor before use if you have a breathing problem such as chronic bronchitis," highlighting that diphenhydramine is not appropriate for routine respiratory complaints. 3

• Diphenhydramine has anticholinergic properties that can theoretically worsen bronchospasm and increase mucus viscosity, making it potentially harmful in patients with obstructive airway disease. 2

Dangerous Sedative Effects in Respiratory Compromise

• Diphenhydramine causes significant sedation and CNS depression, which can mask worsening respiratory distress or lead to respiratory depression itself. 2, 3, 4

• The drug's sedative effects are particularly dangerous when combined with other CNS depressants, and marked drowsiness is a predictable adverse effect that could compromise a patient's ability to maintain adequate ventilation. 3, 4

• A case report documented cardiac arrest in a 3-month-old infant immediately following IV diphenhydramine administration for sedation, demonstrating the potential for catastrophic cardiovascular and respiratory collapse. 5

When Diphenhydramine May Be Appropriate (With Critical Caveats)

Anaphylaxis Only—As Second-Line Therapy

• In anaphylaxis presenting with respiratory distress (laryngeal edema, bronchospasm), diphenhydramine 1-2 mg/kg or 25-50 mg parenterally is considered second-line therapy to epinephrine and should NEVER be administered alone. 1

• Epinephrine is the only first-line treatment for anaphylaxis; there is no absolute contraindication to epinephrine administration in anaphylaxis. 1

• The combination of diphenhydramine with ranitidine is superior to diphenhydramine alone in anaphylaxis management, but both have much slower onset of action than epinephrine. 1

• For bronchospasm resistant to adequate doses of epinephrine in anaphylaxis, consider inhaled β-agonist (nebulized albuterol 2.5-5 mg) rather than relying on diphenhydramine. 1

Acute Allergic Reactions (Not Life-Threatening)

• For mild allergic reactions with urticaria or angioedema causing minor respiratory symptoms (nasal congestion, mild throat irritation), diphenhydramine may be appropriate, but second-generation antihistamines are preferred due to fewer side effects. 6

• Urticaria and angioedema in isolation are not anaphylaxis and do not constitute an indication for aggressive treatment. 1

Algorithm for Decision-Making

Step 1: Identify the Cause of Respiratory Distress

• If anaphylaxis (acute onset, urticaria, angioedema, hypotension, bronchospasm): Give epinephrine 0.3-0.5 mg IM immediately, then consider diphenhydramine 25-50 mg IV/IM as adjunct. 1

• If asthma exacerbation, COPD, pneumonia, pulmonary embolism, heart failure, or any non-allergic cause: Do NOT give diphenhydramine—treat the underlying condition with appropriate bronchodilators, oxygen, diuretics, antibiotics, etc. 2, 3

• If mild allergic rhinitis or urticaria without respiratory compromise: Consider second-generation antihistamines (cetirizine, loratadine) over diphenhydramine due to superior safety profile. 6

Step 2: Assess for Contraindications

• Do not use diphenhydramine in patients with:
  • Active bronchospasm or wheezing from asthma/COPD (anticholinergic effects may worsen bronchospasm) 2
  • Altered mental status or decreased level of consciousness (sedation will worsen respiratory drive) 2, 3
  • Hypotension (diphenhydramine can cause further hypotension) 7, 8
  • Elderly patients with cognitive impairment (risk of delirium and anticholinergic crisis) 7, 8

Step 3: Monitor Continuously if Diphenhydramine is Given

• Continuous monitoring is mandatory until the patient is awake and ambulatory, including vital signs (blood pressure, respiratory rate, oxygen saturation). 7

• Watch for paradoxical agitation (especially in children), hypotension, urinary retention, and anticholinergic crisis. 7, 8

• The 4-6 hour duration of diphenhydramine often exceeds the time needed for symptom control and may delay recognition of worsening respiratory status. 7, 8

Common Pitfalls to Avoid

• Do not use diphenhydramine as monotherapy for any form of respiratory distress—it is not a bronchodilator and will not reverse airway obstruction. 1

• Do not give diphenhydramine to "calm down" an anxious patient with dyspnea—sedation masks the underlying problem and can precipitate respiratory failure. 2, 3

• Do not assume that because diphenhydramine is available over-the-counter, it is safe in respiratory distress—dose-dependent toxicity includes cardiac arrest and death. 5, 9

• Do not delay epinephrine administration in anaphylaxis to give diphenhydramine first—fatalities during anaphylaxis result from delayed epinephrine administration. 1