Allergy and Toxic Reactions to Local Anesthetics

Local anesthesia (LA) forms the foundation of pain control techniques in dentistry. These drugs prevent the passage of noxious stimuli to the patient’s brain where it would be interpreted as painful. Other techniques of pain control are available, including general anesthesia, hypnosis, acupuncture, and electronic dental anesthesia, but none is as consistently reliable and as safe as LA.

Local anesthetics are used more than any other drugs in dentistry. It is conservatively estimated that in excess of 300 million cartridges of LA are administered annually by the dental profession in the United States.1 Each dentist in Canada injects approximately 1,800 cartridges annually.2 Yet, the number of serious complications associated with their administration is extremely low. 

However, problems can and do occur whenever drugs are administered. Problems noted with administration of LAs may be associated with the drug or some other component of the injected LA solution, the act of administering (injecting) the drug, and localized trauma produced by the needle through which the drug is administered.

In this article, 2 of the major complications associated with the administration of LA are reviewed. These are allergy and overdose (toxic reactions).

THE LA CARTRIDGE

 

Figure 1. LA cartridge.
Figure 2. Chemical structure of Articaine HCI.

The LA cartridge is a glass cylinder (plastic cartridges of LA are available in some countries) capable of holding 2.0 mL of solution (Figure 1). A thick silicone rubber stopper (plunger) seals one end of the cartridge. As a result, a filled cartridge contains 1.8 mL of anesthetic solution. (In some countries, such as Great Britain, Australia, and South Africa, LA cartridges contain 2.2 mL). The opposite end of the cartridge has a thin latex membrane through which the needle penetrates into the cartridge.


LA cartridges are manufactured using a process that ensures the solution inside the cartridge is sterile; the outside of the cartridge is aseptic. Changes in Food and Drug Administration (FDA) regulations have added a terminal sterilization step to the manufacturing process of the recently released articaine HCl (Septocaine). The composition of cartridges varies dependent upon whether or not a vasopressor is included in the LA solution (Table 1).

 

 

ALLERGY

LA Allergy

Figure 3. Basic management of all medical emergencies.11

True, documented, and reproducible allergy to ester-type LAs is relatively common, while with amide-type LAs allergy is such a rarity as to be virtually nonexistent3 (Table 2). Reports of “alleged” allergy (eg, “Doctor, I am allergic to Novocain”) are more frequent. Confronted with an alleged LA allergy, the clinician must: (1) always believe the patient and not administer any LA, including (or perhaps, especially) topical anesthetic, and (2) determine what actually happened during their “allergic reaction.” Questions to ask of the patient (dialogue history) are presented in Table 3.

Knowledge of the signs and symptoms of allergy will enable the clinician to quickly differentiate true allergy from the more frequent psychogenic reaction (eg, fainting) or reaction to the vasopressor (epinephrine). When doubt persists in the mind of either the patient or doctor, do not administer any local anesthetic. Definitive allergy testing by an anesthesiologist or allergist may be necessary to determine the true nature of the “reaction.”

 

Allergy to Components of a LA Cartridge

Though allergy to a LA drug is highly unlikely, allergy may occur to one of the components included in the cartridge.


Methyl paraben was included in dental LA cartridges until the mid-1980s when the FDA mandated its removal. Parabens were included in LA cartridges as bacteriostatic agents, maintaining sterility of the solution. As dental LA cartridges are single-use items, there was no need for the inclusion of parabens. However, whenever multidose vials of LAs (or any drug) are employed, methyl paraben will still be present, and allergy to parabens should be considered.

Another component is the antioxidant sodium (meta)bisulfite, which is present in every dental LA cartridge containing a vasopressor (eg, epinephrine, levonordefrin). Potential allergy to bisulfites should be considered if the patient is an allergic-type asthmatic. Bisulfites are also found in many foods and beverages, including dried fruits, cheeses, and wines. In the presence of a documented sulfite allergy it is suggested that a LA solution without a vasopressor (“plain LA”) be used (eg, mepivacaine HCl 3%; prilocaine HCl 4%). There is no cross-allergenicity between sulfites and the “sulfa”-type antibiotics (sulfonimides).4 

 

Specific mention must be made of articaine HCl, an amide local anesthetic that contains a sulfur molecule in its chemical structure (Figure 2). As the sulfur molecule is an integral part of the thiophene ring of articaine HCl, it is not available to act as an allergen. Articaine HCl may safely be administered to patients with sulfur allergy. Introduced in 1975, and presently available in approximately 131 countries, there have been no reported cases of allergy to articaine HCl.5

Epinephrine Allergy
Allergy to epinephrine cannot occur. Questioning of the “epinephrine-allergic” patient (see dialogue history, above) immediately reveals signs and symptoms related to increased blood levels of circulating catecholamines (tachycardia, palpitation, sweating, nervousness), likely the result of fear of receiving injections (release of endogenous catecholamines [epinephrine and norepinephrine]).

Latex Allergy

The thick plunger (also known as the “stopper”) on one end of the LA cartridge and the thin diaphragm on the other end of the cartridge (Figure 1) through which the needle penetrates may contain latex. As latex allergy is of growing concern among all healthcare professionals, the risk of provoking an allergic reaction in a latex-sensitive patient must be considered. A recent review of the literature on latex allergy and local anesthetic cartridges by Shojaei and Haas6 demonstrates that latex allergen can be released into the LA solution as the needle penetrates the diaphragm, but there were no reports or case studies in which an allergic response to the latex component of the cartridge containing a dental local anesthetic was documented.

OVERDOSE (TOXIC REACTIONS)
Overdose (also known as toxic reaction) occurs when the blood (serum) level of LA in either the central nervous system (CNS) or myocardium is elevated to a point where the drug produces potentially life-threatening events. The overdose reaction persists until the blood level of the drug in these “target” organs falls below the toxic level. Table 4 lists ways in which overly high blood levels can be produced. 

In Table 4, the first 3 listings represent the most common causes of local anesthetic overdose in dentistry. 

Intravenous administration may be prevented by always performing an aspiration test prior to and during all LA injections. Of somewhat greater importance is the rate at which the LA is administered. The ideal rate of drug administration is 1 mL per minute. Recommended for dental offices is a rate not to exceed 1 cartridge (1.8 mL) per minute. 

The administration of too large a local anesthetic dose in relation to the age and weight of the patient is the most common cause of serious overdose of LAs in dentistry. Though some serious cases of LA overdose have occurred in adult patients,7 the overwhelming majority of problems have developed in children, commonly the child who is younger (2 to 6 years), lighter-weight (15 to 40 kg), well-behaved, requiring multiple procedures in 4 quadrants, and managed in the office of an inexperienced general dentist.

Review of many of the cases that resulted in serious morbidity or death reveals a number of shared factors, none of which by themselves might pose a serious problem, but when taken together act to produce clinical signs and symptoms of LA overdose. Some of these factors are presented in Table 5. 

As listed in Table 5, the factors adding to increased risk of LA overdose in younger patients are...
(1) Treatment plan. In interviews with trained pediatric dentists, I have found that when presented with the patient described above (young, light-weight, well-behaved), the pediatric dentist will not treat all 4 quadrants at one visit using LA. Limiting treatment to 1 or 2 quadrants per visit represents a more rational approach to this patient’s needs, and increased safety.

The dentist who is confronted with a (well-meaning) parent or grandparent who complains of the difficulties of getting to the dental office and the inconvenience of having to miss a half day of work, and wanting to have their child’s dental care accomplished in one visit (not two or more), might feel pressured into agreeing to this request, thus increasing the risk for LA overdose.
(2) Choice of LA. In most instances where serious LA overdose has occurred in children, the LA administered has been a “plain” drug, either mepivacaine HCl 3% or prilocaine HCl 4%. Both of these are excellent LAs when used properly. The rationale behind the clinician’s selection of a short-acting drug for children includes: (a) most pediatric appointments are of short duration, and (b) plain LAs have a shorter duration of posttreatment soft tissue anesthesia, minimizing the likelihood of inadvertent soft tissue injury as the child bites or chews his/her numb lip or tongue.

As a rule, the pediatric dentist will administer a plain LA only when treatment is limited to one quadrant. When treatment extends to 2 quadrants or more in one visit, a vasopressor-containing LA will be selected. Prolonged post-treatment soft tissue anesthesia does lead to the increased possibility of soft tissue damage, however, this risk is far outweighed by benefits accrued through delayed absorption of both the LA and vasopressor into the cardiovascular system (the risk of overdose is diminished). There are many ways of preventing postoperative soft-tissue injury, such as securing a cotton roll in the buccal fold and advising the parent to watch the child.
(3) Volume of LA administered. Pain control for the entire primary dentition can be achieved with approximately 2 cartridges of LA. In the child patient, there is never a compelling reason to administer a full 1.8 mL cartridge of LA for any 1 injection. Yet, when children receive LA administered by nonpediatric dentists, full cartridges tend to be routinely administered. In many of the instances where death resulted, a total of 5, 6, or 7 cartridges were administered.8

In cases where LA must be administered to all 4 quadrants of a younger child, this can be achieved with no more than 2 cartridges, as follows: either one-quarter cartridge each for the right- and left-incisive nerve blocks (anesthetizing all mandibular teeth), or one-third cartridge each for right- and left-inferior alveolar nerve blocks; and one-third cartridge each for the right- and left-anterior superior alveolar nerve blocks. In lieu of the anterior superior alveolar nerve block, maxillary infiltrations may be administered with one-sixth cartridge per injection (Table 6).
(4) LA administered to all 4 quadrants at one time. The administration, over 1 or 2 minutes, of 4 or more cartridges of a LA without a vasopressor to all 4 quadrants makes little therapeutic sense, while increasing the likelihood of an overdose. Administration of LA to one quadrant, treating that area, then anesthetizing the next quadrant, and so on, makes considerably more sense both from a therapeutic and safety perspective. For equal amounts of LA, administration over a longer timeframe (1 to 2 hours) will result in a lower blood level of the LA as compared to the entire dose being administered at one time.
(5) Exceeding the maximum dosage based on patient’s body weight. An important factor, especially when managing younger, lighter-weight patients, is maximum dosage. Determine the weight of the patient (in pounds [lb] or kilograms [kg]) prior to the start of treatment. It is preferable to weigh the child on a scale, as parents frequently can offer only a rough estimate of the child’s weight.

Maximum recommended dosages of commonly administered LAs are presented in Table 7. 

The intrinsic safety of LAs is illustrated in Table 8, which presents the volume of LA administered on 65 occasions by a general dentist who removed third molars from college-aged individuals. None of these patients experienced an adverse response to the LA although many received dosages 2 or more times maximum recommended dose.10 This is one indication that local anesthetics are extremely safe drugs, when administered to healthy, adult patients. Unfortunately, when administered in overly large doses to younger, light-weight patients, overdose is a significant risk.

Virtually all LA overdose reactions are preventable if the clinician adheres to the very basic, simple recommendations presented above. In the unlikely situation where an overdose reaction develops, adherence to the basic steps of emergency management (Figure 3) will lead to a successful outcome in virtually all cases.

 

CONCLUSION
LAs are the foundation of pain control in dentistry and are used to reversibly block peripheral nerve conduction. It must always be remembered that all drugs have the potential to do harm. All dentists and hygienists permitted to administer LAs must be aware of these potential problems and be prepared to manage them expeditiously and effectively.


References

  1. Malamed SF. What’s new in local anaesthesia: dentistry’s first line in pain control. Independent Dentistry. 2001;4:43-46.
  2. Haas D, Lennon D. Local anesthetic use by dentists in Ontario. J Can Dent Assoc. 1995;61:297-304.
  3. Jastak JT, Yagiela JA, Donaldson D. Local Anesthesia of the Oral Cavity. Philadelphia, Pa: Saunders; 1995.
  4. Haas DA. An update on local anesthetics in dentistry. J Can Dent Assoc. 2002;68:546-551.
  5. Malamed SF, Gagnon S, Leblanc D. Articaine hydrochloride: a study of the safety of a new amide local anesthetic. J Am Dent Assoc. 2001;132:177-185.
  6. Shojaei AR, Haas DA. Local anesthetic cartridges and latex allergy: a literature review. J Can Dent Assoc. 2002;68:622-626.
  7. Malamed SF. Morbidity, mortality and local anaesthesia. Primary Dental Care. 1999;6:11-15.
  8. Finder RL, Moore PA. Adverse drug reactions to local anesthesia. Dent Clin North Am. 2002;46:747-757.
  9. Malamed SF. Handbook of Local Anesthesia. 4th ed. St Louis, Mo: C.V. Mosby Inc; 1997:191, 218, 265.
  10. Malamed SF. Report of a case. Unpublished data. 2002.
  11. Malamed SF. Handbook of Medical Emergencies in the Dental Office. 5th ed. St. Louis, Mo: C.V. Mosby Inc; 2000:51-52.

Dr. Malamed is a professor of anesthesia and medicine at the School of Dentistry at the University of Southern California.


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