hich could include other local anesthetics: examples of drugs associated with methemoglobinemia: class examples nitrates/nitrites nitric oxide, nitroglycerin, nitroprusside, nitrous oxide local anesthetics articaine, benzocaine, bupivacaine, lidocaine, mepivacaine, prilocaine, procaine, ropivacaine, tetracaine antineoplastic agents cyclophosphamide, flutamide, hydroxyurea, ifosfamide, rasburicase antibiotics dapsone, nitrofurantoin, para-aminosalicylic acid, sulfonamides antimalarials chloroquine, primaquine anticonvulsants phenobarbital, phenytoin, sodium valproate other drugs acetaminophen, metoclopramide, quinine, sulfasalazine

overall prevalence of sulfite sensitivity in the general population is unknown and probably low. sulfite sensitivity is seen more frequently in asthmatic than in non asthmatic people. the american heart association has made the following recommendations regarding the use of local anesthetics with vasoconstrictors in patients with ischemic heart disease: “vasoconstrictor agents should be used in local anesthesia solutions during dental practice only when it is clear that the procedure will be shortened or the analgesia rendered more profound. when a vasoconstrictor is indicated, extreme care should be taken to avoid intravascular injection. the minimum possible amount of vasoconstrictor should be used.” (kaplan, el, editor: cardiovascular disease in dental practice, dallas 1986, american heart association.) methemoglobinemia cases of methemoglobinemia have been reported in association with local anesthetic use. although all patients are at risk for methemoglobinemia, patients with glucose-6-phosphate dehydrogenase deficiency, congenital or idiopathic methemoglobinemia, cardiac or pulmonary compromise, infants under 6 months of age, and concurrent exposure to oxidizing agents or their metabolites are more susceptible to developing clinical manifestations of the condition. if local anesthetics must be used in these patients, close monitoring for symptoms and signs of methemoglobinemia is recommended. signs of methemoglobinemia may occur immediately or may be delayed some hours after exposure, and are characterized by a cyanotic skin discoloration and/or abnormal coloration of the blood. methemoglobin levels may continue to rise; therefore, immediate treatment is required to avert more serious central nervous system and cardiovascular adverse effects, including seizures, coma, arrhythmias, and death. discontinue 2% xylocaine dental and any other oxidizing agents. depending on the severity of the signs and symptoms, patients may respond to supportive care, i.e., oxygen therapy, hydration. a more severe clinical presentation may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.

anesthetic agents, like sedatives, are central nervous system depressants which in combination may have an additive effect. young children should be given minimal doses of each agent. lidocaine should be used with caution in patients with severe shock or heart block. lidocaine should also be used with caution in patients with impaired cardiovascular function. local anesthetic solutions containing a vasoconstrictor should be used with caution in areas of the body supplied by end arteries or having otherwise compromised blood supply. patients with peripheral vascular disease and those with hypertensive vascular disease may exhibit exaggerated vasoconstrictor response. ischemic injury (such as exfoliating or ulcerating lesions) or necrosis may result. preparations containing a vasoconstrictor should be used with caution in patients during or following the administration of potent general anesthetic agents, since cardiac arrhythmias may occur under such conditions. cardiovascular and respiratory (adequacy of ventilation) vital signs and the patient’s state of consciousness should be monitored after each local anesthetic injection. restlessness, anxiety, tinnitus, dizziness, blurred vision, tremors, depression or drowsiness should alert the practitioner to the possibility of central nervous system toxicity. signs and symptoms of depressed cardiovascular function may commonly result from a vasovagal reaction, particularly if the patient is in an upright position: placing the patient in the recumbent position is recommended when an adverse response is noted after injection of a local anesthetic (see adverse reactions - cardiovascular system .) vasovagal reactions may elicit a range of clinical manifestations, from prodrome signs of pre-syncope (e.g. lightheadedness, pallor, nausea, sweating, visual disturbances, weakness) to brief loss of consciousness (i.e. syncope). lidocaine should be used with caution in patients with hepatic disease, since amide-type local anesthetics are metabolized by the liver. patients with severe hepatic disease, because of their inability to metabolize local anesthetics normally, are at greater risk of developing toxic plasma concentrations. many drugs used during the conduct of anesthesia are considered potential triggering agents for familial malignant hyperthermia. since it is not known whether amide-type local anesthetics may trigger this reaction, and since the need for supplemental general anesthesia cannot be predicted in advance, it is suggested that a standard protocol for management should be available. early unexplained signs of tachycardia, tachypnea, labile blood pressure and metabolic acidosis may precede temperature elevation. successful outcome is dependent on early diagnosis, prompt discontinuance of the suspected triggering agent(s) and prompt treatment, including oxygen therapy, dantrolene (consult dantrolene sodium intravenous package insert before using) and other supportive measures. lidocaine should be used with caution in persons with known drug sensitivities. patients allergic to para-aminobenzoic acid derivatives (procaine, tetracaine, benzocaine, etc.) have not shown cross sensitivity to lidocaine.

basis. in oral infiltration and/or mandibular block, initial dosages of 1.0 - 5.0 ml (½ to 2 ½ cartridges) of 2% xylocaine dental (lidocaine hci 2% solutions with a 1:50,000 or a 1:100,000 epinephrine concentration) are usually effective. in children under 10 years of age, it is rarely necessary to administer more than one-half cartridge (0.9 - 1.0 ml or 18 - 20 mg of lidocaine) per procedure to achieve local anesthesia for a procedure involving a single tooth. in maxillary infiltration, this amount will often suffice to the treatment of two or even three teeth. in the mandibular block, however, satisfactory anesthesia achieved with this amount of drug, will allow treatment of the teeth of an entire quadrant. aspiration is recommended since it reduces the possibility of intravascular injection, thereby keeping the incidence of side effects and anesthetic failures to a minimum. moreover, injection should always be made slowly. maximum recommended dosages for 2% xylocaine dental (lidocaine hci 2% solutions with a 1:50,000 or a 1:100,000 epinephrine concentration). adult for normal healthy adults, the amount of lidocaine hci administered should be kept below 500 mg, and in any case, should not exceed 7 mg/kg (3.2 mg/lb) of body weight. pediatric pediatric patients it is difficult to recommend a maximum dose of any drug for pediatric patients since this varies as a function of age and weight. for pediatric patients of less than ten years who have a normal lean body mass and normal body development, the maximum dose may be determined by the application of one of the standard pediatric drug formulas (e.g., clark’s rule). for example, in pediatric patients of five years weighing 50 ibs, the dose of lidocaine hydrochloride should not exceed 75 - 100 mg when calculated according to clark’s rule. in any case, the maximum dose of lidocaine hydrochloride should not exceed 7 mg/kg (3.2 mg/lb) of body weight. note: parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever the solution and container permit. solutions that are discolored and/or contain particulate matter should not be used and any unused portion of a cartridge of 2% xylocaine dental should be discarded.

tory manifestations may be very brief or may not occur at all, in which case the first manifestation of toxicity may be drowsiness merging into unconsciousness and respiratory arrest. drowsiness following the administration of lidocaine is usually an early sign of a high blood level of the drug and may occur as a consequence of rapid absorption. cardiovascular system cardiovascular manifestations in response to lidocaine are usually depressant and are characterized by bradycardia, hypotension, and cardiovascular collapse, which may lead to cardiac arrest. in addition, the beta-adrenergic receptor-stimulating action of epinephrine may lead to excitatory cardiovascular responses, such as tachycardia, palpitations, and hypertension. signs and symptoms of depressed cardiovascular function may commonly result from a vasovagal reaction, particularly if the patient is in an upright position. less commonly, they may result from a direct effect of the drug. failure to recognize the premonitory signs such as sweating, a feeling of faintness, changes in pulse or sensorium may result in progressive cerebral hypoxia and seizure or serious cardiovascular catastrophe. management consists of placing the patient in the recumbent position and ventilation with oxygen. supportive treatment of circulatory depression may require the administration of intravenous fluids and, when appropriate, a vasopressor (e.g, ephedrine) as directed by the clinical situation. allergic reactions allergic reactions are characterized by cutaneous lesions, urticaria, edema, anaphylactoid reactions, or dyspnea due to bronchoconstriction. allergic reactions as a result of sensitivity to lidocaine are extremely rare and, if they occur, should be managed by conventional means. the detection of sensitivity by skin testing is of doubtful value. neurologic reactions the incidences of adverse reactions (e.g., persistent neurologic deficit) associated with the use of local anesthetics may be related to the technique employed, the total dose of local anesthetic administered, the particular drug used, the route of administration, and the physical condition of the patient. persistent paresthesias of the lips, tongue, and oral tissues have been reported with the use of lidocaine, with slow, incomplete, or no recovery. these post-marketing events have been reported chiefly following nerve blocks in the mandible and have involved the trigeminal nerve and its branches.

hich could include other local anesthetics: examples of drugs associated with methemoglobinemia: class examples nitrates/nitrites nitric oxide, nitroglycerin, nitroprusside, nitrous oxide local anesthetics articaine, benzocaine, bupivacaine, lidocaine, mepivacaine, prilocaine, procaine, ropivacaine, tetracaine antineoplastic agents cyclophosphamide, flutamide, hydroxyurea, ifosfamide, rasburicase antibiotics dapsone, nitrofurantoin, para-aminosalicylic acid, sulfonamides antimalarials chloroquine, primaquine anticonvulsants phenobarbital, phenytoin, sodium valproate other drugs acetaminophen, metoclopramide, quinine, sulfasalazine

inephrine concentration) or 2% xylocaine dental with epinephrine 1:100,000 (lidocaine hci 2% solution with a 1:100,000 epinephrine concentration) provide pulp anesthesia averaging at least 90 minutes with an average duration of soft tissue anesthesia of 3 to 3 ½ hours. hemodynamics excessive blood levels may cause changes in cardiac output, total peripheral resistance, and mean arterial pressure. these changes may be attributable to a direct depressant effect of the local anesthetic agent on various components of the cardiovascular system and/or the beta-adrenergic receptor stimulating action of epinephrine when present. pharmacokinetics and metabolism information derived from diverse formulations, concentrations and usages reveals that lidocaine is completely absorbed following parenteral administration, its rate of absorption depending, for example, upon various factors such as the site of administration and the presence or absence of a vasoconstrictor agent. except for intravascular administration, the highest blood levels are obtained following intercostal nerve block and the lowest after subcutaneous administration. the plasma binding of lidocaine is dependent on drug concentration, and the fraction bound decreases with increasing concentration. at concentration of 1 to 4 µg of free base per ml, 60 to 80 percent of lidocaine is protein bound. binding is also dependent on the plasma concentration of the alpha-l-acid glycoprotein. lidocaine crosses the blood-brain and placental barriers, presumably by passive diffusion. lidocaine is metabolized rapidly by the liver, and metabolites and unchanged drug are excreted by the kidneys. biotransformation includes oxidative n-dealkylation, ring hydroxylation, cleavage of the amide linkage, and conjugation. n-dealkylation, a major pathway of biotransformation, yields the metabolites monoethylglycinexylidide and glycinexylidide. the pharmacological/toxicological actions of these metabolites are similar to, but less potent than those of lidocaine. approximately 90% of lidocaine administered is excreted in the form of various metabolites, and less than 10% is excreted unchanged. the primary metabolite in urine is a conjugate of 4-hydroxy-2, 6-dimethylaniline. studies of lidocaine metabolism following intravenous bolus injections have shown that the elimination half-life of this agent is typically 1.5 to 2.0 hours. because of the rapid rate at which lidocaine is metabolized, any condition that affects liver function may alter lidocaine kinetics. the half-life may be prolonged two-fold or more in patients with liver dysfunction. renal dysfunction does not affect lidocaine kinetics but may increase the accumulation of metabolites. factors such as acidosis and the use of cns stimulants and depressants affect the cns levels of lidocaine required to produce overt systemic effects. objective adverse manifestations become increasingly apparent with increasing venous plasma levels above 6.0 µg free base per ml. in the rhesus monkey, arterial blood levels of 18 - 21 µg/ml have been shown to be the threshold for convulsive activity.

drug are excreted by the kidneys. biotransformation includes oxidative n-dealkylation, ring hydroxylation, cleavage of the amide linkage, and conjugation. n-dealkylation, a major pathway of biotransformation, yields the metabolites monoethylglycinexylidide and glycinexylidide. the pharmacological/toxicological actions of these metabolites are similar to, but less potent than those of lidocaine. approximately 90% of lidocaine administered is excreted in the form of various metabolites, and less than 10% is excreted unchanged. the primary metabolite in urine is a conjugate of 4-hydroxy-2, 6-dimethylaniline. studies of lidocaine metabolism following intravenous bolus injections have shown that the elimination half-life of this agent is typically 1.5 to 2.0 hours. because of the rapid rate at which lidocaine is metabolized, any condition that affects liver function may alter lidocaine kinetics. the half-life may be prolonged two-fold or more in patients with liver dysfunction. renal dysfunction does not affect lidocaine kinetics but may increase the accumulation of metabolites. factors such as acidosis and the use of cns stimulants and depressants affect the cns levels of lidocaine required to produce overt systemic effects. objective adverse manifestations become increasingly apparent with increasing venous plasma levels above 6.0 µg free base per ml. in the rhesus monkey, arterial blood levels of 18 - 21 µg/ml have been shown to be the threshold for convulsive activity.

eratures and pressures. if chemical disinfection of anesthetic cartridges is desired, either isopropyl alcohol (91%) or 70% ethyl alcohol is recommended. many commercially available brands of rubbing alcohol, as well as solutions of ethyl alcohol not of u.s.p grade, contain denaturants that are injurious to rubber and, therefore, are not to be used. it is recommended that chemical disinfection be accomplished just prior to use by wiping the cartridge cap thoroughly with a pledget of cotton that has been moistened with recommended alcohol. certain metallic ions (mercury, zinc, copper, etc.) have been related to swelling and edema after local anesthesia in dentistry. therefore, chemical disinfectants containing or releasing these ions are not recommended. antirust tablets usually contain sodium nitrite or some similar agents that may be capable of releasing metal ions. because of this, aluminium sealed cartridges should not be kept in such solutions. quaternary ammonium salts, such as benzalkonium chloride, are electrolytically incompatible with aluminium. cartridges of 2% xylocaine dental are sealed with aluminium caps and therefore should not be immersed in any solution containing these salts. to avoid leakage of solutions during injection, be sure to penetrate the center of the rubber diaphragm when loading the syringe. an off-center penetration produces an oval shaped puncture that allows leakage around the needle.other causes of leakage and breakage include badly worn syringes, aspirating syringes with bent harpoons, the use of syringes not designed to take 1.7 ml cartridges, and inadvertent freezing. cracking of glass cartridges is most often the result of an attempt to use a cartridge with an extruded plunger. an extruded plunger loses its lubrication and can be forced back into the cartridge only with difficulty. cartridges with extruded plungers should be discarded. store at controlled room temperature, below 25°c (77°f).