TOXCARD: Diphenhydramine to the rescue, useful for more than hives

Author: Brian P. Murray, DO (@bpatmurray Senior EM Resident Physician, Resident Brooke Army Medical Center) // Edited by: Cynthia Santos, MD (Senior Medical Toxicology Fellow, Emory University School of Medicine), Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UT Southwestern Medical Center / Parkland Memorial Hospital), and Brit Long, MD (@long_brit)



A 22-year-old man presents to the Emergency Department with a simple laceration to his right arm that needs sutures. Upon further questioning, the patient states he is allergic to both lidocaine and tetracaine.



What medication can be used in the of setting of amide and ester allergies?



Diphenhydramine is an effective alternative at producing local anesthesia through local infiltration due to its sodium channel blocking effects.


Amide analgesic allergy:

  • Allergic reactions to amide analgesics (e.g. lidocaine, bupivacaine, mepivacaine) are very rare, but a potential for a severe life threatening anaphylactic reaction does exist. [5]
  • More common than a true lidocaine allergy is an allergy to methylparaben, a preservative in multi-use vials. [5]
  • Traditionally, if a patient is allergic to amides, ester anesthetics (e.g. procaine, tetracaine) are used, however these agents degrade to para-amino benzoic acid, a chemical similar to methylparaben. Thus, “allergic reactions” to both amides and esters are possible. [5]


  • Memory Trick: Amide anesthetics have to i’s while ester anesthetics only have 1 i.
    • ex. lidocaine has 2 i’s so it’s an amide while tetracaine has 1 i so it is an ester.


Role of antihistamines as a local anesthetic:

  • Local infiltration of antihistamines has been studied as an anesthetic since the 1930s. [1]
  • 1% diphenhydramine is as effective as 2% procaine at producing local anesthesia in order to perform minor surgical procedures. [2]
  • 1% diphenhydramine is as effective as 1% lidocaine as a local anesthetic up to 30 minutes, although the duration of anesthesia is greater with lidocaine. [3,4,5,6]
  • 80% of patients will attain sufficient pain control 5 minutes after infiltration of 1% diphenhydramine. [7]
  • To make a 1% (10mg/mL) diphenhydramine solution mix 40mL of normal saline with 10mL of 5% (50mg/mL) diphenhydramine.
  • Diphenhydramine owes its analgesic properties to its ability to block sodium channels.
  • Despite its ability to produce analgesia, local infiltration of diphenhydramine can be more painful than infiltration of either lidocaine or normal saline. [4,6]
  • Side effects range from drowsiness (>2.5mL) [8] to skin sloughing typically with a 5% solution [5,8] and local necrosis [3], but these events are relatively rare.
  • The dose of 1% diphenhydramine needed to attained anesthesia is similar (~4mL) to that needed for 1% lidocaine. [9]


Main Point:

True allergies to amide and ester anesthetics are rare, but potentially life threatening. More often preservatives are the cause of local reactions or allergies, but it is near impossible to distinguish these reactions prior to the initiation of a local procedure requiring anesthesia. Diphenhydramine has been shown to be an effective alternative to amide and ester anesthetics.



  1. Rosenthal SR, Minard D. Experiments on histamine as the chemical mediator for cutaneous pain. The Journal of experimental medicine. 1939 Oct 1;70(4):415-25.
  2. STEFFEN CG, ZIMMERMAN M, MIHAN R. Diphenhydramine hydrochloride as a local anesthetic agent. AMA Arch Derm. 1956 Jul;74(1):76–9.
  3. Dire DJ, Hogan DE. Double-blinded comparison of diphenhydramine versus lidocaine as a local anesthetic. YMEM. 1993 Sep;22(9):1419–22.
  4. Green SM, Rothrock SG, Gorchynski J. Validation of diphenhydramine as a dermal local anesthetic. YMEM. 1994 Jun;23(6):1284–9.
  5. Bartfield JM, Jandreau SW, Raccio-Robak N. Randomized Trial of Diphenhydramine Versus Benzyl Alcohol with Epinephrine as an Alternative to Lidocaine Local Anesthesia. YMEM. Elsevier; 1998 Dec 1;32(6):650–4.
  6. Ernst AA, Anand P, Nick T, Wassmuth S. Lidocaine versus diphenhydramine for anesthesia in the repair of minor lacerations. Journal of Trauma and Acute Care Surgery. 1993 Mar 1;34(3):354-7.
  7. Gallo WJ, Ellis E., 3 Efficacy of diphenhydramine hydrochloride for local anesthesia before oral surgery. J Am Dent Assoc. 1987;115(2):263–266
  8. Pavlidakey PG, Brodell EE, Helms SE. Diphenhydramine as an alternative local anesthetic agent. The Journal of clinical and aesthetic dermatology. 2009 Oct;2(10):37.
  9. Ernst AA, Marvez-Valls E, Mall G, Patterson J, Xie X, Weiss SJ. 1% lidocaine versus 0.5% diphenhydramine for local anesthesia in minor laceration repair. Annals of emergency medicine. 1994 Jun 30;23(6):1328-32.



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