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Diphenhydramine (Benadryl)

Anesthesia Implications

Updated On: July 10, 2026

Classification:
First-generation H1-antihistamine (ethanolamine), anticholinergic
Therapeutic Effects:
Antihistamine, antiemetic, sedative, anticholinergic, antipruritic, treatment of dystonic reactions
Time to Onset:

IV - within minutes; IM - 15-30 min

Time to Peak Effects:

1-3 hours

Duration:

4-6 hours

Primary Considerations:

Sedation additive - Potentiates opioids, benzodiazepines, and volatile agents; anticipate deeper sedation and slower emergence, especially in the elderly.

Dystonia rescue - First-line for acute drug-induced dystonic/extrapyramidal reactions (e.g., from metoclopramide, droperidol) at 25-50 mg IV.

Anaphylaxis adjunct - Useful adjunct for allergic reactions but is NOT a substitute for epinephrine in anaphylaxis.

Anticholinergic load - Adds to the central anticholinergic burden; contributes to postoperative delirium and urinary retention in older patients.

Drug Interactions - Additive CNS depression with sedatives and alcohol; additive anticholinergic effect with atropine, glycopyrrolate, and tricyclics; may mask aminoglycoside ototoxicity.

Pediatric Implications - Weight-based (1.25 mg/kg, max 50 mg); paradoxical excitation is common. Avoid in neonates.

Obstetric Implications - Category B; crosses the placenta. Used for pruritus and nausea in pregnancy; large peripartum doses may cause neonatal sedation. Small amounts in breast milk.

Contraindications:

Relative:

Narrow-angle glaucoma

Bladder-neck obstruction / BPH

Neonates

Caution:

Elderly (delirium, falls)

Asthma with thick secretions

IV push dose:

25-50 mg IV for allergic reactions, PONV, or dystonia (adult); 1.25 mg/kg, max 50 mg (pediatric).

IM dose:

25-50 mg IM.

Method of Action:

Competitive reversible antagonist at central and peripheral H1 receptors; also blocks muscarinic receptors, producing anticholinergic and antiemetic effects.

Metabolism:

Hepatic

Elimination:

Renal

Additional Notes:

Give IV slowly (25 mg/min). Marked sedation; caution with outpatient/day-surgery discharge and driving.

Reference

Sicari V, Zabbo CP. Diphenhydramine. StatPearls. Updated 2023.link
Gan TJ, Belani KG, Bergese S, et al. Fourth consensus guidelines for the management of postoperative nausea and vomiting. Anesth Analg. 2020;131(2):411-448.link
American Geriatrics Society 2023 Updated AGS Beers Criteria. J Am Geriatr Soc. 2023;71(7):2052-2081.link
Gan TJ, Belani KG, Bergese S, et al. Fourth Consensus Guidelines for the Management of PONV. Anesth Analg. 2020;131(2):411-448. (diphenhydramine 50 mg).link