Allergic Reaction to Epinephrine Preparation in 2% Lidocaine

In: Anesthesia

23 Sep 2009

Epinephrine preparations are composed of artificial chemical products that have the same chemical and pharmacokinetic characteristics as endogenous epinephrine in vivo. Local anesthetics with epinephrine are commonly used in dentistry to provide effective anesthesia, good hemostasis, and to prevent toxic reaction to local anesthetics. Systemic complications to local anesthetics with epinephrine are well documented, but few cases of *allergic reaction to epinephrine have been reported.

We report 2 cases of allergic reactions (*Generic Zyrtec preventing or treating allergic symptoms), found by skin tests, to an epinephrine preparation for local anesthetics.


Case 1

A male, 48-year-old patient consulted our clinic to be examined for an allergic reaction to local anesthetics.

Ten years earlier, he was administered a local anesthetic (drug name unknown) by a dentist. Immediately after the injection, he complained of severe palpitations and dysphoria. Since the episode, he has not received any local anesthetics. He had no other past history except for cholecystitis. We found no abnormalities during physical evaluation and 12-lead electrocardiogram examinations.

We performed the drug lymphocyte stimulating test (DLST) on the patient using 2% lidocaine with 1: 80,000 epinephrine, 3% prilocaine with 0.03 IU/mL of felypressin, and 0.5% bupivacaine. The test showed negative results to all agents. Blood and serum findings were normal.

Table 1. Results of Skin Tests to 2% Lidocaine with 1:80,000 Epinephrine and Epinephrine Preparation

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Diluted Concentration

1:80,000 Epinephrine


1:100                             1:10

Case 1 Case 2 Negative Positive Positive*                 Positive* Positive                 Not performed

Diluted Concentration



1:50,000                  1:25,000

Case 1 Positive Positive                 Positive
* Positive criteria in skin test: more than 20 mm in diameter of erythrogenic or pseudobranch or more than 30 mm in diameter of erythrogenic region.

Next, we performed skin tests using 2% lidocaine with 1:80,000 epinephrine, 3% prilocaine with felypressin, and 2% lidocaine. These anesthetics were diluted to 1:1000, 1:100, and 1:10 with saline solution for the skin test, respectively. Doses of 0.02 mL of these diluted agents were injected subcutaneously in the forearm skin and the same dose of vehicle was injected in the same manner on the contralateral forearm skin as control. These results are summarized in Table 1. Marked wheals with pseudobranches appeared in 1: 100 and 1:10 diluted solutions of 2% lidocaine with epinephrine. The size of the wheals was more than 30 mm in length and 25 mm in width.

Based on these results, the skin tests of 1:100,000, 1: 50,000 and 1: 25,000 diluted solutions of epinephrine preparation (BOSUMIN) were performed, respectively. The results are shown in Table 1. Approximately 30 minutes after the intracutaneous injections, marked erythrogenic reactions (more than 30 mm width and length) around the ischemic zones were found on the patient’s forearm in all responding sites. They remained for about 120 minutes. He complained of an itching sensation on his forearms, but no other abnormal incidences were observed. Positive reaction to epinephrine preparation was strongly suggested by this skin test. viagra online pharmacy

We again performed the DLST for 1:80,000 solution of epinephrine preparation (BOSUMIN). The result of the test was negative, with the stimulation index (SI) 106%. Seven days later, we once again performed the DLST for each epinephrine preparation component (epinephrine hydrochloride, epinephrine bitartrate, chlorbutanol, and sodium hydrogensulfate) in order to identify the origin of the abnormal reactions of these skin tests. The final concentrations of the components used in the DLST were 0.0125 mg/mL of epinephrine hydrochloride, epinephrine bitartrate, 0.6 mg/mL of sodium hydrogen sulfate, 0.001 mg of chlorbutanol, 2% lidocaine, 2% lidocaine with 1:80,000 epinephrine, and 3% prilocaine with 0.03 IU/mL of felypressin.

Table 2. Values of Stimulation Index in Drug Lymphocytes Stimulating Test (DLST)

Epine phrine Sodium Hydro-
Epinephrine Hydrochloride Bitar-trate Chlor-butanol gensul-fate
Case 1 554%*




Case 2 Not performed




The tests revealed positive reactions to epinephrine hydrochloride with SI 554%, and epinephrine bitartrate with SI 496%, false-positive reaction to sodium hydrogensulfate with SI 190%, and negative reaction to chlorbutanol with SI 139% (Table 2).

As a result of these findings, we preferred local anesthetics without epinephrine for dental treatment in order to avoid an allergic reactions (Atarax 25 mg is used to treat allergic reactions) to epinephrine. Thereafter, the patient was administered 1 mL of 2% lidocaine and 3% prilocaine with felypressin for the intraoral mucosa, respectively. Dental treatment was completed without complications.

Case 2

A 14-year-old female was injected with local anesthetics (drug name unknown) into her oral mucosa by a dentist and, 2 hours later, developed edema in the zygomatic region that continued for about 2 days. She was referred to our clinic by the dentist. She reported 1 other occurrence of edema of the conjunctiva and lip after taking medication (drug name unknown). She reported no other abnormal past history. No abnormalities were found in physical state.

We performed skin tests for 2% lidocaine (1:1000, 1:100, 1:10 diluted solution and undiluted solution), 2% lidocaine with 1:80,000 epinephrine (1:1000, 1: 100 diluted solution), and 3% prilocaine with felypressin (1:1000, 1:100, 1:10 diluted solution). Table 1 shows the results. Wheals surrounded with rubor appeared in 1:1000, 1:100 diluted solutions of 2% lidocaine with epinephrine. We noted the reaction to 2% lidocaine with epinephrine and made a positive diagnosis for this skin test. Negative results were obtained in other agents.

Next we performed the DLST for each epinephrine preparation component (the concentrations of each component were the same as those used in case 1). The tests revealed positive reaction to epinephrine bitartrate, with SI 679%, and negative reactions to sodium hydrogensulfate, with SI 124%, and chlorbutanol, with SI 103%.

Because the patient showed a positive reaction to epinephrine, 3% prilocaine with felypressin was administered for dental treatment. Dental treatment proceeded without complication./td

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