Allergy to Local Anesthesia
True immunoglobin-E mediated allergic reactions to local anesthetics are rare. Many patients and clinicians mistake any idiosyncratic response after local anesthetic injection for an allergic reaction. Giovanitti and Bennett estimated that no more than 1 percent of the adverse reactions to local anesthesia is true allergy.43 However, once reactive to an antigen, the patient is allergic to this drug for the rest of his or her life.
The immunoglobin-E allergic reaction is acquired through exposure to an antigen. With re-exposure, the antigen-antibody response is heightened until a point where mast cells respond with the release of chemical mediators that produce the clinical manifestations of allergy. These mediators include histamines, leukotrienes, chemotactic substances, Iysozomal enzymes, prostaglandins, kinins, and platelet-activating factor. 44, 45These mediators cause capillaries to leak and permit extravasation of plasma into the surrounding area. True drug allergies manifest as asthma, rhinitis, angioneurotic edema, urticaria, and rash. Urticaria is caused by release of histamine, which induces peripheral capillary leakage along with erythema, pruritis, and edema. Immunoglobin-E anaphylaxis may be severe enough to cause respiratory distress and cardiovascular collapse. Anaphylaxis is the result of a generalized increase in capillary permeability leading to a drop in blood pressure. Furthermore, released leukotrienes cause bronchiolar smooth muscle to spasm, eliciting an asthmatic-type response.
No matter how doubtful their claim, treat all patients as "allergic to local anesthetics" until the patient is allergy-tested.
Allergy Signs and Symptoms
Mild signs of an allergic reaction include urticaria and rash. Urticaria is associated with pruritis (itching) and wheals (elevated skin patch). These mild dermatological signs are usually visible within six minutes. As the allergic reaction progresses, the cardiovascular, respiratory and gastrointestinal systems become involved. Hypotension is the initial cardiovascular response. Increased histamine release during allergy causes increased plasma extravasation to the interstitial tissues leading to a decrease in blood pressure and to generalized angioneurotic edema. Angioedema typically involves the face, hands, feet, and genitalia. During severe cases, the lips, tongue, larynx, and pharynx are also involved. Angioedema of the upper tracheobronchial tree (laryngeal edema) induces stridor by limiting air exchange to and from the lungs.
Wheezing would be indicative of bronchospasm. Bronchospasm and asthmatic-type reactions are the result of leukotrienes. Leukotrienes, similar to histamines, are chemical mediators that cause sudden contraction of the bronchial smooth muscle. Other symptoms of bronchospasm may include dyspnea, wheezing, flushing, cyanosis, tachycardia, and increased use of accessory muscles of respiration.
Predisposing Factors to Allergy
Many patients claim allergies to Novocain. Ester-type local anesthetics, i.e., procaine, chloroprocaine, and tetracaine, are derived from paraamino benzoic acid, a known allergen. Furthermore, when ester local anesthetics are hydrolyzed by plasma cholinesterase, its metabolites include para-amino benzoic acid. Amide local anesthetics are almost entirely devoid of this problem. After years of countless carpules of amide local anesthetics being administered, only a few cases have been reported with an amide local anesthetic challenge.46
Older commercial preparations of local anesthetics included preservatives, such as methylparaben. Methylparaben is chemically related to paraamino benzoic acid and is also identified as an allergen.47 Methylparaben is a bacteriostatic agent found in many drugs, cosmetics, and foods. Currently, methylparaben has been removed from dental local anesthetic cartridges but is still found in multiple dose vials.
Another preservative used is sodium bisulfite or metabisulfite. Bisulfites are antioxidants used to prevent the early breakdown of epinephrine in dental cartridges. No allergic reactions to dental cartridges without epinephrine have been reported. Bisulfites are also found in food, preventing the food from "browning" (oxidizing) when exposed to air. Most patients who are intolerant to bisulfites are also dependent upon inhaled steroids to prevent acute episodes of bronchospasm.
Treatment of Allergic Reaction
Delayed mild cases of an allergic reaction are usually treated by 50 mg of intravenous, intramuscular or oral diphenhydramine (Benadryl). Followup doses of 50 mg oral diphenhydramine every four hours is recommended for three days.
If the initial signs of anaphylaxis proceed to conjunctivitis, rhinitis, urticaria, pruritis, and erythema within 60 minutes, 50 mg of IM diphenhydramine (25 mg for a child) and/or 0.3 mg of intramuscular epinephrine (0.15 mg for a child) is recommended. Corticosteroids, such as dexamethasone or methylprednisone, are effective in decreasing edema and capillary permeability. Intravenous 8 mg of dexamethasone (4 mg for a child) should be considered if the condition appears to be imminent. When speed is not a factor, Medrol Dosepak is an oral corticosteroid of choice. Subsequently, Benadryl should be prescribed orally for three to four days as precaution.
Bronchospasm or allergic asthma is treatable if diagnosed early. The patient will typically complain of difficulty in breathing and expresses a desire to sit upright. Wheezing may be heard with air exchange. For an asthmatic response, aerosolized albuterol or Medihaler-Epi is considered the first line of treatment.14 Intramuscular antihistamines, like diphenhydramine 50 ma, may also be beneficial. If aerosol or antihistamine treatments are not effective or the patient is unconscious, 0.3 mg intramuscularly of epinephrine will activate the beta-2-agonist receptor sites causing bronchodilation. If these treatments are ineffective or the episode recurs, activate emergency medical services. Medical consultation and followup with a physician is recommended.
Although no known cases of anaphylaxis to an amide local anesthetic have occurred within 30 minutes, prevention and immediate intervention is important, especially with laryngeal edema. Laryngeal edema is the one of the most ominous events following an initial allergic reaction. Immediate attention should be paid to evaluation of the patency of the airway. Complete obstruction of the larynx results in no sound and air passage. If a highpitched crowing sound is heard the airway is partially obstructed. Either obstruction requires the same treatment. Emergency medical services should be immediately activated. Administer 0.3 mg of intramuscular epinephrine and maintain a patent airway with bag, mask, and supplemental oxygen. Intravenous steroids and histamineblockers are also recommended. If the patient does not improve, consider opening an air passage below the obstruction. Typically this involves cricothyrotomy.8, 14
Fortunately, anaphylaxis to an amide local anesthetic in a dental office is nearly non-existent. However, generalized anaphylaxis is one of the most urgent emergencies in the dental office. Most of the signs and symptoms have a rapid onset and significant morbidity. In most cases, the patient will be come cyanotic and lose consciousness within minutes. All of the above symptoms with laryngeal edema, bronchospasm, and cardiovascular collapse may occur simultaneously. Unless treatment is immediate, the mortality rate is extremely high. Following airway maintenance, intravenous 0.3 mg epinephrine is the first line of treatment; followed by 8 mg dexamethasone. Assisted ventilation with supplemental oxygen is recommended. Management of the cardiovascular component of the reaction requires 15 mg of intravenous ephedrine to combat the severe hypotension, which is often present.8 Chest compressions, may be necessary if the patient is pulseless. Activation of emergency medical services is important, however basic life support is the most important step in successful management of anaphylaxis. Prompt and definitive treatment may be the difference of life and death.
Due to the rarity of local anesthetic allergy, the simplest in vivo allergy testing technique is recommended. The probability of an anaphylactic response is minimal, especially with the intracutaneous testing technique. However, with any allergy testing, a specialist should complete the testing with an intravenous line started and emergency equipment and drugs at the ready.
Due to the morbidity and mortality involved with toxicity studies, most clinical studies involve animals. Few case presentations of toxicity and allergy in humans have been reported. The dosages necessary to produce toxicity and allergy vary between species; however, there is a direct correlation between animals and humans with respect to central nervous and cardiovascular system toxicity.
Local anesthetics are central nervous system depressants. At critical low blood levels, their depressant effects can be therapeutic in the prevention of certain types of seizures. At higher blood levels, the suppression of inhibitory pathways results in facilitatory pathways functioning unopposed, resulting in seizures. At very high blood levels, the facilitatory pathways also are blocked, resulting in complete suppression of the central nervous system. This condition is associated with coma and depression of respiratory and circulatory centers ultimately leading to death.
The cardiovascular system tends to be more resistant to the toxic effects. Local anesthetics have a suppressant effect on the heart, reducing myocardial contractile force and prolonging or blocking intracardiac conduction. They are also vasodilators. High doses of local anesthetics cause a reduction in heart rate and blood pressure, cardiac conduction defects, and arrhythmias, including ventricular tachycardia and fibrillation. There is, for the most part, a separation between the dose and blood concentration required to cause central nervous and cardiovascular system toxicity.
In general, the cardiotoxic and neurotoxic effects of local anesthetics do not differ greatly, but their relative potential for toxicity does. At certain dosages, bupivacaine produces effects different from those of other local anesthetics. There is considerable evidence to support the contention that bupivacaine exerts a strong direct effect on the myocardium and the brain.
The treatment of systemic toxicity due to local anesthetics should be instituted rapidly and aggressively. Appropriate equipment and pharmacological agents should be kept close at hand. Maintenance of an open airway and administration of oxygen is important. Support of the circulation and control of arrhythmias are essential for maintaining adequate perfusion of the vital organs as well as assisting in the removal of local anesthetic from the tissue and its detoxification. Persistence in the resuscitation process is essential, as some patients may prove difficult to resuscitate.
Allergic reactions to local anesthetics agents are extremely rare. Ester local anesthetics produce para-amino benzoic acid as a metabolite, and it is a known allergen. Methylparaben is also a known allergen, and it is used occasionally as a preservative in commercial preparations of some amide local anesthetics. Reactions are generally dermatologic when they occur and rarely are systemic or anaphylactoid. Recommendations for screening suspect patients can be found in the literature and generally involve skin tests.
The intent of this article is to review the pharmacology of the local anesthetics and the mechanisms to toxicity and allergy. A good knowledge of the pharmacokinetics and pharmacodynamics of local anesthetics is important; both the patient and the practitioner should have a proper understanding of the consequences of local anesthesia administration. Early intervention can be started when all persons involved know the initial signs and symptoms of toxicity and allergy. Precaution is the best prevention, whether it is overdose toxicity or allergy; and knowledge is the first key to prevention.
تم تعديل هذه المشاركة بواسطة hamza_ju: 05/03/2011 - 17:42