How to Address Patients with a Documented Lidocaine Allergy

DECEMBER 16, 2015
Local anesthetics inhibit the influx of sodium ions, thus interrupting neuronal conduction. For this reason, they are commonly used for minor procedures in the primary care setting.
 
Lidocaine is preferably used due its availability in a co-formulation with epinephrine. On rare occasions, however, patients may present with a documented lidocaine allergy.

There are 2 classes of local anesthetics, amides and esters. Esters include benzocaine, chloroprocaine, cocaine, procaine, proparacaine, and tetracaine. The amides include articaine, bupivacaine, levobupivacaine, dibucaine, etidocaine, mepivacaine, prilocaine, ropivacaine, and finally, lidocaine.

The majority of patient-reported allergies to local anesthetics are not immune-mediated reactions. In fact, only about 1% actually are.1

Of the immune-mediated reactions, Type I hypersensitivity occurs within minutes and is mediated by immunoglobulin E (IgE).2 It is mainly due to the components of local anesthetics, methylparaben, a preservative in multi-dose vials, and sulfites in select products, which act as antioxidants. Type IV reactions are delayed and are more commonly implicated with local anesthetic molecules themselves.

Some of the ester local anesthetics are similar in structure to sulfonamide antibiotics, with a para-substituted benzene ring being part of the chemical structure. When these drugs are metabolized, they liberate para-aminobenzoicacid (PABA). As a parent molecule to methylparaben, PABA may be the culprit of the hypersensitivity reaction; however, it is inappropriate to assume cross-reactivity with sulfonamide antibiotics and methylparaben or other para-substituted benzene-containing molecules.2

Solutions of local anesthetics containing vasopressors (eg, epinephrine) typically contain sulfites. These, on the other hand, are usually cross-reactive with other substances containing sulfites (eg, wine and select preserved foods).2

Because local anesthetics are small molecules themselves, they lack specific chemical properties typically seen in those that are immunogenic, such as the large molecule size seen in animal-derived proteins (eg, albumin, heparin, insulin) and molecules possessing multiple valences.2 These types of small molecules are known as haptens, or incomplete allergens.
 
Haptens require complexing with proteins such as albumin to elicit IgE production through immune response; however, no data support this mechanism with local anesthetics.3

Challenging a patient’s history of documented allergy by administering the implicated drug may not be feasible or ethical in the primary care setting, where comprehensive equipment may not be readily available to manage anaphylactic reactions, specifically those involving the airway.
 
Allergists may perform epidermal, intradermal, or subcutaneous tests to elucidate true hypersensitivity reactions.4 Such services may not be available on demand and patients may not be willing to incur additional cost for a medication they may seldom need, especially if alternatives are available.

Though occasionally employed in patients who have a true allergy to a medication expected to be needed long term, sensitization protocols may not be practical or necessary for a patient requiring a one-time dose for a procedure.

Even though lidocaine is not thought to be cross-reactive with other amides based anesthetics on skin tests, there has been documentation of positive cross-reactivity of a lidocaine allergy with mepivicaine and ropivacaine, but not bupivacaine.5 It is even less common for cross-reactivity of a lidocaine allergy with ester-based local anesthetics, specifically chlorprocaine.
 
Further research is necessary to evaluate truly non-cross-reactive local anesthetics to reduce possible patient harm and lead to better decision-making in the clinic.

References
1. Liu W, Yang X, Li C, Mo A. Adverse drug reactions to local anesthetics: a systematic review. Oral Surg Oral Med Oral Pathol Oral Radiol. 2013 Mar;115(3):319-27.
2. Becker DE, Reed KL. Local anesthetics: review of pharmacological considerations. Anesth Prog. 2012 Summer;59(2):90-102.
3. Parslow TG, Stites DP, Terr AI, et al. Medical Immunology. (10th ed.). New York: McGraw-Hill, 2001:394-9.
4. Speca SJ, Boynes SG, Cuddy MA. Allergic reactions to local anesthetic formulations. Dent Clin N Am. 2010 Oct;54(4):655-64.
5. Redfern DC. Contact sensitivity to multiple local anesthetics. J Allergy Clin Immunol. 1999 Oct;104(4 Pt 1):890-1.

Patrick Wieruszewski, PharmD
Patrick Wieruszewski, PharmD
Patrick M. Wieruszewski, PharmD, is a Critical Care Pharmacist at Mayo Clinic in Rochester, Minnesota. He graduated from the University of Florida in 2016 with subsequent completion of a PGY-1 Pharmacy Residency and PGY-2 Critical Care Residency at Mayo Clinic in Rochester, Minnesota. His interests include pulmonary and critical care medicine, immunocompromised hosts, medical writing, and clinical research.
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