Montana Anesthesia Services

Benadryl (Diphenhydramine) in Anesthesia

Benadryl, known generically as diphenhydramine, is an antihistamine medication commonly used to treat allergic reactions, insomnia, and motion sickness 1. However, its utility extends beyond these applications, as diphenhydramine is also useful in anesthesia. Understanding the uses, effects, and considerations associated with Benadryl in anesthesia is essential for healthcare professionals to ensure safe and effective patient care.

In anesthesia practice, Benadryl serves multiple purposes based on its pharmacological properties. First off, its antihistamine properties are particularly useful 2. Diphenhydramine’s antihistamine effects make it useful for preventing and treating allergic reactions during anesthesia, particularly those involving histamine release secondary to medications, surgical procedures, or other allergens. Secondly, it is useful for sedation 3. Benadryl possesses sedative properties, which can aid in premedication before anesthesia induction, helping to alleviate preoperative anxiety and promote relaxation in patients. Third, Benadryl has antiemetic effects 4. Its antiemetic properties make it beneficial in preventing nausea and vomiting associated with anesthesia and surgery, particularly in susceptible patients. Finally, Benadryl can be used as an adjunctive analgesic across clinical contexts 5. Although not primarily indicated as an analgesic, Benadryl may provide mild pain relief as an adjunctive therapy in certain anesthesia settings.

Patients who present with a history of allergy to local anesthetics are common in clinical practice 6. Injectable 1% diphenhydramine represents a cheap, safe, and effective local anesthetic for simple dermatological procedures in patients who report “-caine” allergies. Studies have demonstrated that diphenhydramine 1% is as effective as lidocaine 1% for achieving dermal local anesthesia, although injection may be more painful 7,8. Using Benadryl can allow the dermatologist to operate at the time of the initial visit and schedule a referral to the allergist for definitive sensitivity testing at the patient’s convenience.

When administered as part of an anesthesia regimen, Benadryl can exert various effects on a patient’s physiology. These include but are not limited to central nervous system depression, anticholinergic effects, cardiovascular effects, and respiratory depression.

While Benadryl can be a valuable adjunct in anesthesia practice, several considerations and precautions are important to keep in mind 9. Individual patient characteristics, including age, comorbidities, concurrent medications, and drug allergies, should guide the selection and dosing of diphenhydramine; elderly patients and those with preexisting cardiovascular or respiratory conditions may be more susceptible to adverse effects. In addition, careful attention should be paid to the dosage and route of administration of diphenhydramine, with weight-based dosing and slow titration to minimize the risk of adverse reactions. Close monitoring of vital signs, sedation levels, and adverse effects is essential to swiftly identify and manage any complications that may arise. Diphenhydramine through its drug interactions may potentiate the effects of other central nervous system depressants, including opioids, benzodiazepines, and anesthetics. Overall, healthcare providers need to be well-educated about and mindful of potential drug interactions and adjust dosages accordingly to avoid excessive sedation or respiratory depression.

Benadryl plays a valuable role in anesthesia practice, offering antihistamine, sedative, antiemetic, and adjunctive analgesic effects. However, its use requires careful consideration of patient factors, dosing, administration, and potential adverse effects. By understanding the pharmacological properties and clinical implications of diphenhydramine in anesthesia, healthcare providers can optimize its use to enhance patient comfort and safety throughout the perioperative period.


1. Benadryl Oral: Uses, Side Effects, Interactions, Pictures, Warnings & Dosing – WebMD. Available at: (Accessed: 12th February 2024).

2. About Diphenhydramine HCl: The Active Ingredient in BENADRYL® | BENADRYL®. Available at: (Accessed: 12th February 2024).

3. Diphenhydramine: drowsy (sedating) antihistamine – NHS. Available at: (Accessed: 12th February 2024)

4. Antiemetic Histamine H1 Receptor Blockers – StatPearls – NCBI Bookshelf. Available at: (Accessed: 12th February 2024).

5. Santiago-Palma, J., Fischberg, D., Kornick, C., Khjainova, N. & Gonzales, G. Diphenhydramine as an analgesic adjuvant in refractory cancer pain. J. Pain Symptom Manage. (2001). doi:10.1016/S0885-3924(01)00311-6.

6. Pavlidakey, P. G., Brodell, E. E. & Helms, S. E. Diphenhydramine as an alternative local anesthetic agent. J. Clin. Aesthet. Dermatol. (2009).

7. Green, S. M., Rothrock, S. G. & Gorchynski, J. Validation of Diphenhydramine as a Dermal Local Anesthetic. Ann. Emerg. Med. (1994). doi:10.1016/S0196-0644(94)70353-1.

8. Dire, D. J. & Hogan, D. E. Double-blinded comparison of diphenhydramine versus lidocaine as a local anesthetic. Ann. Emerg. Med. (1993). doi:10.1016/S0196-0644(05)81989-4.

9. Benadryl: Uses, Dosage & Side Effects – Available at: (Accessed: 12th February 2024).