Allergic Response to Metabisulftte in Lidocaine Anesthetic Solution: DISCUSSION

In: Anesthesia

3 Jan 2010


This patient had 3 injections of lidocaine with epinephrine solution within 5 days by 3 different dentists. The incision and drainage was performed with the presumptive diagnosis of an abscess. The elevated white blood cell count was minimal and would be considerably more elevated (ie, greater than 20,000) if an abscess were the etiology. The only exception would be an infection in an immunocompromised patient such as someone who has AIDS or is taking steroids.

Local anesthetics are generally classified into either esters or amides. The esters include benzocaine, chloroprocaine, cocaine, procaine, propoxycaine, and tet-racaine. These local anesthetics are recognized to have a greater incidence of allergic responses than amides. Cholinesterase found in the plasma and liver metabolizes these esters and forms a metabolite called p-amino-benzoic acid (PABA). PABA, which is highly antigenic, is the most likely cause of allergic reactions to the ester anesthetics. The amide group includes bupivicaine, di-bucaine, etidocaine, lidocaine, mepivacaine, and prilo-caine. Preservatives or other substances in these anesthetic solutions or the amide compound itself may cause an allergic reaction. Methylparaben, the preservative agent in a multidose vial with or without epinephrine, is also metabolized to PABA. Therefore, patients who are allergic to PABA theoretically may show cross-reactivity between methylparaben-containing solutions of ester and amide groups. Although uncommon, other substances, such as the antioxidants, may produce an allergic response. These antioxidants, which are found in anesthetic solutions that contain vasoconstrictors, include metabisulfite and sodium bisulfite. Last, in rare cases, an immunologic reaction to an amide anesthetic may be caused by the amide linkage itself. canadian antibiotics

Additionally, a new local anesthetic was marketed in the United States as of August 2000. This anesthetic, articaine, is classified as an amide, but it has both amide and ester linkages. Articaine also contains the vasoconstrictor epinephrine, metabisulfite, and a sulfur atom in the thiophene ring. Therefore, patients with metabisulfite allergies should not be given articaine. To complicate the situation further, one reference states that a patient with a sulfa allergy is an absolute contraindication to articaine. However, the package insert does not list sulfa allergy as a contraindication. More investigation is needed to see if those patients with adverse responses to esters and true sulfa allergies are at risk when administered articaine.

Allergic reactions are classified into 4 categories based on the immune system antigen-antibody response. Types I, II, and III are immediate-type reactions, and Type IV is a delayed-type reaction. Type I reactions manifest as anaphylaxis. The first exposure to the anesthetic is the sensitizing dose. It causes immunoglobulin E (IgE) antibody production from type В lymphocyte cells and these antibodies bind to basophils and mast cells. On exposure to a second dose of the agent, the antigen binds to the antibodies, causing basophils and mast cells to release inflammatory mediators such as cytokines and histamine.

Type I hypersensitivity reactions may be life threatening. Treatment depends on severity and can include oxygen; intravenous fluids; subcutaneous, intramuscular, or intravenous epinephrine, steroids, and antihistamines; and even endotracheal airway management.

Type II reactions involve primarily IgG or IgM anti bodies directed against antigens on an individual’s own cells. Hemolysis and agranulocytosis can occur with Type II.
Type HI reactions involve antigen-antibody complexes that are not removed by the reticuloendothelial system. The complexes deposit in blood vessel walls, causing vascular and connective tissue damage.

Type IV (delayed-type hypersensitivity) reactions are the most common with local anesthetics. Type T lymphocyte cells are sensitized to the local anesthetic during first exposure (no antibodies are formed). On a secondary exposure, the memory T cells release lymphokines that cause inflammatory reactions and activate macrophages to release mediators of inflammatory reactions. Symptoms of Type IV reactions are similar to those of Type I. These include erythema, swelling, and uticaria. However, these are generally localized to the region of injection.
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Most reactions to local anesthetics are not true allergies; rather, they are autonomic or toxic adverse affects. It may be difficult to distinguish between immediate allergic reactions and autonomic adverse effects. Systemic symptoms present as tachycardia, sweating, and hypotension, which may or may not result in a loss of consciousness. In contradistinction, syncope-induced hypotension can occur in patients with fear of receiving injections. However, autonomic affects are short lived and usually require minimal treatment. Toxic reactions occur when excessive amounts of a local anesthetic are given or an inadvertent intravascular injection has occurred. Symptoms of systemic toxicity include dizziness, muscle twitching, diplopia, tremor, bradycardia, decreased cardiac output, and seizures. If the practitioner cannot discern whether the reaction was autonomic, toxic, skin testing should be performed. To date, immunoassays have been less than diagnostic. Many medications can modify an allergic response to skin testing. These include antihistamines, cough and cold medications, tricyclic antidepressants, and steroids, all of which should be discontinued for several days prior to testing.


The 22-year-old female is presumed to be allergic to the preservative sodium metabisulfite, which is present in local anesthetics that have a vasoconstrictor present. While the patient does not suffer specifically from a lidocaine allergy, she does manifest a moderately severe reaction to the antioxidant that would be present in any drug accompanying a vasoconstrictor such as epinephrine or levonordefrin. Under the assumption that, if a patient were to present to any dental office with a strong

history of an allergic reaction, especially verified by a physician who removed moles, as described by this patient, a practitioner should do one of the following: (1) refer the patient for evaluation, which may or may not include allergy testing, or (2) use an agent other than the one the patient stated she was allergic to, including the preservative and antioxidant.
A history of certain food allergies may be an indicator of a metabisulfite allergy. Allergies to sodium bisulfite and metabisulfite are not uncommon. Bisulfites are antioxidants commonly sprayed on fruits and vegetables at salad bars to keep them fresh. Sulfites are also added to bottled wines to prevent oxidation.
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The patient tested negative for lidocaine plain with methylparaben present as the preservative. It is important to note that, if the patient had tested positive in this group, a second test involving lidocaine plain from a dental cartridge and lidocaine plain from a multidose vial would have been necessary to rule out a methylparaben allergy. As dental practitioners, we do not generally consider methylparaben allergies because this preservative was eliminated from dental cartridges in 1984. Physicians and many oral and maxillofacial surgeons utilize multidose vials of local anesthetics; therefore, one needs to consider methylparaben as an allergen when a history of allergy to local anesthetics is present.

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