Mechanisms of Action for Anesthetics

Most dental pharmacology courses teach that local anesthetics block sodium channels by partitioning into two types, the uncharged basic form of the molecule (RN), which crosses cell membranes, and the charged acid form of the molecule (RNH ⁺ ), which binds to the inner pore of the sodium channel. As a first approximation, this model is reasonably accurate. However, molecular research has demonstrated the existence of at least nine subtypes of voltage-gated sodium channels (VGSCs) that differ in their expression pattern, biophysical properties, and roles in mediating peripheral pain ( Table 4-1 ). These channels have a clear clinical relevance. Indeed, several groups of patients have been described with genetic mutations to a VGSC, with significant reported effects on pain sensitivity.

The broad class of VGSCs can be divided into channels that are blocked by a toxin (tetrodotoxin [TTX]) and those that are resistant to the toxin (TTX-R). Most TTX-R channels are found primarily on nociceptors (e.g., Na _v 1.8 and Na _v 1.9). These channels also are relatively resistant to local anesthetics and are sensitized by prostaglandins. As is explained later in the chapter, the presence of TTX-R sodium channels may explain why local anesthetics are less effective when administered to patients with odontalgia. Many of the adverse effects of local anesthetics are attributed to their ability to block other VGSCs expressed in the central nervous system (CNS) or heart (see Table 4-1 ).

VGSCs consist of an alpha and a beta subunit. The alpha subunit serves as a voltage sensor, leading to channel activation and sodium ion passage when the channel detects an electrical field. The biologic basis for an electrical pulp tester, therefore, is the generation of a small electrical field across the dental pulp that can activate VGSCs. Interestingly, sensitization of TTX-R channels by prostaglandins lowers the activation threshold and increases the number of sodium ions that flow through the channel. Put another way, an inflammation-induced elevation in prostaglandin levels sensitizes TTX-R channels, leading to greater activation with weaker stimuli. This may explain the increased responsiveness to electrical pulp testing seen in patients with irreversible pulpitis.

Local anesthetics have other mechanisms that may contribute to their pharmacology for treating odontogenic pain. For example, local anesthetics modulate certain G protein–coupled receptors (GPCRs). The GPCRs are a major class of cell membrane receptors, and many classes of dental drugs (e.g., opioids, catecholamines) and endogenous mediators produce their effects by activating specific GPCRs and their related second messenger pathways. Studies suggest that local anesthetics inhibit the G-alpha-q (G _{α q} ) class of GPCRs, which includes receptors activated by inflammatory mediators such as bradykinin. Local anesthetics may therefore block the actions of a major hyperalgesic agent.

Other studies have indicated that local anesthetics potentiate the actions of the G-alpha-i (G _{α i} ) class of GPCRs. This could have a major effect in potentiating the actions of vasoconstrictors, including the newly recognized analgesic role that vasoconstrictors play in inhibiting pulpal nociceptors. Prolonged alteration of GPCR function might explain why analgesia obtained with long-acting local anesthetics persists well beyond the period of anesthesia. More research is needed on this exciting aspect of local anesthetic pharmacology.

Clinically Available Local Anesthetics

The most common forms of injectable local anesthetics are in the amide class. In 2003, the American Dental Association specified a uniform color code for dental cartridges to prevent confusion among brands ( Table 4-2 ). Local anesthetics can be divided roughly into three types: short duration (30 minutes of pulpal anesthesia), intermediate duration (60 minutes of pulpal anesthesia), and long duration (over 90 minutes of pulpal anesthesia). However, clinical anesthesia does not always follow these guidelines, depending on whether the local anesthetic is used as a block or for infiltration. For example, bupivacaine is classified as a long-acting agent, and when it is used in an inferior alveolar nerve (IAN) block, this is true. However, when it is used for infiltration for anterior teeth, it has a shorter duration of anesthetic action than 2% lidocaine with 1 : 100,000 epinephrine (this is discussed in more detail later in the chapter).

Selection of a Local Anesthetic: Possible Adverse Effects, Medical History, and Preoperative Anxiety

Possible Adverse Effects

Possible adverse reactions to local anesthetics can be divided into six major categories: cardiovascular reactions, systemic effects, methemoglobinemia, peripheral nerve paresthesia, allergic reactions to the anesthetic and/or latex, and reactions to anesthetics containing a sulfite antioxidant. These reactions range from fairly common (e.g., tachycardia after intraosseous injection of 2% lidocaine with 1 : 100,000 epinephrine) to extremely rare (e.g., allergic reactions to lidocaine).

Cardiovascular Reactions

Although classic research studies have reported that large dosages or intravenous (IV) injections of local anesthetics were required to produce cardiovascular effects, it now is well recognized that even comparatively small amounts of epinephrine can induce measurable tachycardia after nerve block or intraosseous injection. Several authors have reported increases in heart rate with infiltration injections and nerve blocks using 2% lidocaine with 1 : 100,000 epinephrine ; others have reported that no significant changes in heart rate occurred or that the changes were clinically insignificant. When specific information was given on dosing and heart rate increases, several studies found mean heart rate increases. Two studies found increases on average of about 4 beats/min with approximately 20 µ g of epinephrine ; three studies recorded increases of 10 to 15 beats/min with 45 to 80 µ g of epinephrine ; and one study found increases of approximately 21 beats/min using 144 µ g. Increasing the amount of epinephrine in an infiltration or block injection, therefore, increases the likelihood of an elevated heart rate.

Tachycardia after injection is primarily a pharmacologic effect. The cardiovascular effects are the result of alpha-adrenoceptor stimulation by systemic distribution of the vasoconstrictor throughout the vascular compartment. The patient may also report heart palpitations associated with anxiety or fear and may experience transient tachycardia and changes in blood pressure. Large doses or inadvertent IV injection may lead to lidocaine toxicity and CNS depression. To reduce this risk, the clinician should always aspirate before making the injection, inject slowly, and use dosages within accepted guidelines. The maximal dosages for local anesthetics are listed in Table 4-2 .

Systemic Effects

Acute toxicity from an overdose of a local anesthetic often is the result of inadvertent IV administration or of a cumulative large dose (e.g., repeated injections). As shown in Table 4-1 , VGSCs are found in the CNS and the myocardium, the two major sites of anesthetic-induced toxicity. Although systemic effects from a local anesthetic are rare, they can include an initial excitatory phase (e.g., muscle twitching, tremors, grand mal convulsions) and a subsequent depressive phase (e.g., sedation, hypotension, and respiratory arrest). It should be noted that symptomatic management (possibly including cardiopulmonary resuscitation [CPR], airway support, and supplemental oxygen) is the primary response to this adverse event. An acute hypotensive crisis with respiratory failure also has been interpreted as the result of hypersensitivity to local anesthetics ; these patients should be evaluated with allergy testing. To reduce the risk of systemic effects from anesthetics, the clinician must always aspirate before giving the injection and must use dosages within accepted guidelines (see Table 4-2 ). Finder and Moore proposed a “rule of 25” as a simple means of remembering maximal local anesthetic dosages: with currently formulated local anesthetic cartridges, it generally is safe to use one cartridge of local anesthetic for every 25 pounds of patient weight (e.g., six cartridges for a patient weighing 150 pounds [67.5 kg]).

Methemoglobinemia

Metabolism of certain local anesthetics (e.g., prilocaine, benzocaine, articaine, and to a lesser extent lidocaine) can produce a metabolite that causes methemoglobinemia; this effect often occurs several hours after injection of the local anesthetic. Typical signs and symptoms include cyanosis, dyspnea, emesis, and headache. In a study on benzocaine-induced methemoglobinemia, 67% of reported adverse effects of benzocaine were associated with methemoglobinemia; of these events, 93% occurred with spray formulations of benzocaine, and only one case involved the gel formulation. To reduce the risk of methemoglobinemia, clinicians should take care to refrain from giving excessive dosages of local anesthetics.

Peripheral Nerve Paresthesia

Postinjection paresthesia is a rare adverse effect of local anesthetics. The incidence of paresthesia (which involved the lip and/or tongue) associated with articaine and prilocaine was higher than that found with either lidocaine or mepivacaine. Another study evaluated patients referred with a diagnosis of damage to the inferior alveolar and/or lingual nerve that could only have resulted from an IAN block. In 35% of these cases, the paresthesia was caused by a lidocaine formulation, and in 30%, it was caused by an articaine formulation. The conclusion was that there was not a disproportionate nerve involvement from articaine, although this interpretation does not account for large differences in clinical usage of the two local anesthetics. However, with any paresthesia, documentation of the patient’s reported area of altered sensation, the type of altered sensation (e.g., anesthesia, paresthesia, dysesthesia), and regular follow-up are important.

Allergic Reactions to Local Anesthetics and Latex

The amide local anesthetics appear to have little immunogenicity and therefore have an extremely low rate of allergic reactions. One study included more than 140 patients specifically referred for allergy testing because of adverse effects after injection of a local anesthetic; none of these patients had hypersensitivity reactions to intradermal local anesthetics, but case reports of hypersensitivity reactions after administration of local anesthetics have been published. Some concern has been raised that the rubber latex stopper in dental anesthetic cartridges might be a source of allergen to patients allergic to latex. In a review of this literature (1966 to 2001), Shojaei and Haas concluded that some evidence for exposure to the latex allergen exists, although no causal study has been published.

Local anesthetic formulations that contain vasoconstrictors also contain sulfite to prevent oxidation of this agent. Sulfite-induced reactions came to prominence with the report of six deaths after exposure to salad bars or homemade wine. Common reported signs and symptoms include allergic-like reactions, such as urticaria, bronchospasm, and anaphylaxis. Risk factors include an active history of asthma (perhaps 5% of asthmatics are at risk) and atopic allergy. The use of local anesthetics without vasoconstrictors is a possible alternative with these patients. No sulfite reaction in dental practice has ever been documented, possibly because the amount of sulfite in local anesthetic cartridges is relatively small.

Effects of Systemic Diseases or Conditions on Local Anesthetics

It has been stated that vasoconstrictors should be avoided in patients with high blood pressure (higher than 200 mmHg systolic or 115 mmHg diastolic), cardiac dysrhythmias, unstable angina, less than 6 months since myocardial infarction or cerebrovascular accident, or severe cardiovascular disease. However, these conditions are contraindications to routine dental treatment. Patients taking antidepressants, nonselective beta-blocking agents, medicine for Parkinson disease, and cocaine have a potential for problems. In patients taking these medications, plain mepivacaine (3% Carbocaine) can be used for the inferior alveolar nerve block.

Alcoholics have been found to be more sensitive to painful stimulation. Alcoholics with a history of depression/unhappiness may also have reduced pulpal anesthesia. In contrast, alcoholics in recovery may not be at increased risk for inadequate pain control with local anesthesia.

Any of the commonly available local anesthetics are safe for use in pregnant or lactating women. The most important aspect of care with pregnant patients is to eliminate the source of pain by performing the indicated endodontic treatment; this reduces the need for systemic medications.

Local anesthetics may interact with a patient’s medications, so a thorough review of the medical history is an absolute requirement. Potential drug-drug interactions occur primarily with the vasoconstrictors in local anesthetic formulations ( Table 4-3 ). Judicious use of local anesthetic solutions without vasoconstrictors (e.g., 3% mepivacaine) is a reasonable alternative for adult patients.

Studies have found that women try to avoid pain more than men, accept it less, and fear it more. One study found that women find postsurgical pain more intense than males, but men are more disturbed than women by low levels of pain that lasts several days. Another study found gender differences in analgesia for postoperative endodontic pain. Anxiety may also modulate differences in pain responses between males and females. In addition, pain threshold response varies greatly at different stages of the menstrual cycle. Other studies have shown that women report greater pain relief from kappa opioid agonists (e.g., pentazocine) after endodontic treatment. We should be aware that women might react differently to pain than men.

Clinical Anesthesia and Routes of Anesthetic Administration

Recognition is growing that evidence-based therapeutics offers an excellent source of information that should become an aspect of treatment in conjunction with the practitioner’s clinical skills and the patient’s particular needs. In many areas of dentistry, this is a limited concept because few randomized, placebo-controlled, double-blind clinical trials have been conducted. However, this is not the case with dental pharmacology. The astute clinician can make informed decisions on various local anesthetics and routes of injection based on a large collection of well-designed clinical trials. The following discussion focuses on the clinical aspects of local anesthesia, with special emphasis on restorative dentistry and endodontics.

Important Clinical Factors in Local Anesthesia

Traditional Methods of Confirming Anesthesia

Traditional methods of confirming anesthesia usually involve questioning the patient (“Is your lip numb?”), soft tissue testing (e.g., lack of mucosal responsiveness to a sharp explorer), or simply beginning treatment. However, these approaches may not be effective for determining pulpal anesthesia.

Determining Pulpal Anesthesia in Asymptomatic Vital Teeth

Anesthesia in asymptomatic vital teeth can be measured more objectively by applying a cold refrigerant ( Fig. 4-1 ) or by using an electrical pulp tester (EPT), as described in Chapter 1 ( Fig. 4-2 ). Application of cold or the electrical pulp tester can be used to test the tooth under treatment for pulpal anesthesia before a clinical procedure is started.

A cold refrigerant may be used to test for pulpal anesthesia before the start of a clinical procedure.

(Coltène/Whaledent Inc., Cuyahoga Falls, OH.)

An electrical pulp tester also may be used to test for pulpal anesthesia before a clinical procedure is started.

(Courtesy SybronEndo, Corporation Orange, CA.)

Determining Pulpal Anesthesia in Symptomatic Vital Teeth

In symptomatic (painful) vital teeth and after administration of a local anesthetic, testing with a cold refrigerant or an electrical pulp tester can be used to evaluate pulpal anesthesia before an endodontic procedure is started. If the patient responds to the stimulus, pulpal anesthesia has not been obtained, and supplemental anesthetic should be administered. However, in patients presenting for an emergency appointment with a painful vital tooth (e.g., symptomatic irreversible pulpitis), the lack of a response to pulp testing may not guarantee pulpal anesthesia. Therefore, if a patient experiences pain when the endodontic procedure is started, supplemental anesthetic is indicated, regardless of the responsiveness to pulpal testing. If the chamber is necrotic and the canals are vital, no objective test can predict the level of clinical anesthesia.

Patient Who Has Had Previous Difficulty with Anesthesia

Anesthesia is more likely to be unsuccessful in patients who report a history of previous difficulty with anesthesia. These patients generally make comments such as, “Novocaine doesn’t work on me” or “It takes a lot of shots to get my teeth numb.” A good clinical practice is to ask the patient if dentists previously have had difficulty obtaining anesthesia. If the answer is yes, supplemental injections should be considered.

Failure to Achieve Anesthesia in Patients with Pain

Obtaining anesthesia is often difficult in patients with endodontic pain of pulpal origin. A number of explanations have been proposed for this. One is that conventional anesthetic techniques do not always provide profound pulpal anesthesia, and patients with preexisting hyperalgesia may be unable to tolerate any noxious input. Another explanation relates to the theory that inflamed tissue has a lower pH, which reduces the amount of the base form of anesthetic that penetrates the nerve membrane. Consequently, less of the ionized form is available in the nerve to achieve anesthesia. However, this explanation does not account for the mandibular molar with pulpitis that is not readily blocked by an inferior alveolar injection administered at some distance from the area of inflammation. Correlating localized inflammatory changes with failure of the IAN block is difficult.

Another explanation for failure is that nerves arising from inflamed tissue have altered resting potentials and decreased excitability thresholds. Two studies demonstrated that local anesthetics were unable to prevent impulse transmission because of these lowered excitability thresholds. Another factor might be the TTX-R sodium channels, which are resistant to the action of local anesthetics, are increased in inflamed dental pulp, and are sensitized by prostaglandins. A related factor is the increased expression of sodium channels.

Finally, patients in pain are often apprehensive, which lowers the pain threshold. Therefore, practitioners should consider supplemental techniques (e.g., intraosseous injections or periodontal ligament injections ) if an IAN block fails to provide pulpal anesthesia for patients with irreversible pulpitis.

Use of Topical Anesthetics

Fear of needle insertion is a major cause of apprehension in dental patients. Although some studies have demonstrated the effectiveness of topical anesthetics, others have shown no significant pain reduction. Interestingly, one study showed that patients who thought they were receiving a topical anesthetic anticipated less pain regardless of whether they actually received the anesthetic. The most important aspect of a topical anesthetic may not be its clinical effectiveness, but rather its psychological effect on the patient, who believes the practitioner is doing everything possible to prevent pain.

Reversing the Action of Local Anesthetics

Phentolamine mesylate (0.4 mg in a 1.7-ml cartridge [OraVerse, Novalar Pharmaceuticals, San Diego, California]) is a recently developed agent that shortens the duration of soft tissue anesthesia. The duration of soft tissue anesthesia is longer than pulpal anesthesia and is often associated with difficulty eating, drinking, and speaking. The best use of OraVerse is after dental procedures when postoperative pain is not a concern. Asymptomatic endodontic patients may benefit from the use of a reversal agent when they have speaking engagements or important meetings or must perform in musical or theatrical events. Therefore, OraVerse may be used to shorten the duration of soft tissue anesthesia if the patient presents with an asymptomatic tooth and little postoperative pain is anticipated.

Inferior Alveolar Nerve Block for Restorative Dentistry

2% Lidocaine and 1 : 100,000 Epinephrine

Because failure occurs most often with the IAN block, factors that modify mandibular anesthesia must be carefully reviewed. The technique for administering an IAN block can be reviewed in available textbooks. The following discussion reviews the expected outcomes after administration of a conventional IAN block to asymptomatic patients using 1.8 ml of 2% lidocaine with 1 : 100,000 epinephrine (Xylocaine, Lignospan, Octocaine). Although anesthesia requirements vary among dental procedures, the following discussion concentrates on pulpal anesthesia in asymptomatic patients and thus is directly relevant to endodontic therapy.

Anesthetic Success

One way to define anesthetic success for nerve blocks is the percentage of subjects who achieve two consecutive nonresponsive readings on electrical pulp testing within 15 minutes and continuously sustain this lack of responsiveness for 60 minutes. In other words, the objective is to achieve anesthesia within 15 minutes and to have it last 1 hour. This endpoint is as important for restorative dentistry as it is for endodontic treatment, so it is used as a benchmark for clinically significant information from research on local anesthetics. Using this criterion, the percentage of cases in which anesthesia was obtained after IAN block injections ranged from 10% (central incisor) to 65% (second molar). * It is important to note that all patients from these studies reported a positive lip sign (e.g., profound lip numbness); therefore, profound lip numbness does not predict pulpal anesthesia. However, lack of soft tissue anesthesia is a useful indicator that the block injection was not administered accurately for that patient. Missed blocks occur in about 5% of cases, and the clinician should readminister the nerve block before continuing with treatment.

* References .

Anesthetic Failure

Anesthetic failure can be defined as the percentage of subjects who never achieved two consecutive nonresponsive EPT readings at any time during a 60-minute period. Using this criterion, anesthetic failure rates ranged from 17% (second molar) to 58% (central incisor). ^†

† References .

Noncontinuous Anesthesia

Another measure of mandibular anesthesia is noncontinuous anesthesia, which may be related to the action of the anesthetic solution on the nerve membrane (blocking and unblocking the sodium channels). This occurs in about 12% to 20% of patients. ^‡

‡ References .

Slow Onset

After a conventional IAN block injection, the onset of pulpal anesthesia occurs within 10 to 15 minutes in most cases ( Fig. 4-3 ). ^§ Slow onset can be defined as the percentage of subjects who achieved a nonresponsive EPT reading after 15 minutes. In mandibular teeth, slow onset occurs in 12% to 20% of patients.

Incidence of first mandibular molar anesthesia as determined by lack of response to electrical pulp testing at the maximum setting (percentage of 80 readings) across time for 60 minutes.

§ References .

Duration

The duration of action for pulpal anesthesia in the mandible is very good. ^* If patients are anesthetized initially, anesthesia usually persists for approximately hours. Figure 4-3 depicts the time course for complete pulpal anesthesia for an asymptomatic first molar, as defined by the percentage of patients who did not respond to a stimulus (EPT) across time for 60 minutes. Most patients achieved pulpal anesthesia within 15 minutes and had a duration of anesthesia of at least 1 hour, but the success rate was not 100% for the population.

* References .

Alternative Anesthetic Solutions for the Inferior Alveolar Nerve Block

Plain Solutions: 3% Mepivacaine (Carbocaine, Polocaine, Scandonest) and 4% Prilocaine (Citanest Plain)

In a study of volunteers without dental pathosis, anesthesia from IAN injection of 3% mepivacaine plain and 4% prilocaine plain was as effective as that from 2% lidocaine with 1 : 100,000 ( Fig. 4-4 ). A clinical study of patients with irreversible pulpitis also found that 3% mepivacaine and 2% lidocaine with 1 : 100,000 epinephrine were equivalent for IAN blocks. These findings support the selection of 3% mepivacaine as a local anesthetic when medical conditions or drug therapies suggest caution in the administration of solutions containing epinephrine.

Incidence of first mandibular molar anesthesia: comparison of 3% mepivacaine to 2% lidocaine with 1 : 100,000 epinephrine.

Results were determined by lack of response to electrical pulp testing at the maximum setting (percentage of 80 readings) across time for 50 minutes. No significant difference between the two solutions was noted.

4% Prilocaine with 1 : 200,000 Epinephrine (Citanest Forte) and 2% Mepivacaine with 1 : 20,000 Levonordefrin (Carbocaine with Neo-Cobefrin)

In a study of volunteers without dental pathosis, IAN injection of 4% prilocaine with 1 : 200,000 epinephrine or 2% mepivacaine with 1 : 20,000 levonordefrin worked as well as 2% lidocaine with 1 : 100,000 epinephrine in achieving pulpal anesthesia.

Levonordefrin has 75% alpha activity and only 25% beta activity, making it seemingly more attractive than epinephrine (50% alpha activity and 50% beta activity). However, levonordefrin is marketed as a 1 : 20,000 concentration in dental cartridges. Clinically, the higher concentration of levonordefrin makes it equipotent to epinephrine in clinical and systemic effects, so 1 : 20,000 levonordefrin offers no clinical advantage over 1 : 100,000 epinephrine.

Articaine with 1 : 100,000 Epinephrine (Septocaine, Articadent, Zorcaine)

Articaine has been reported to be a safe and effective local anesthetic. It was approved for use in the United States in April, 2000, and is marketed as a 4% solution with either 1 : 100,000 or 1 : 200,000 epinephrine. Articaine is classified as an amide. It has a thiophene ring (instead of a benzene ring, as do the other amide local anesthetics) and an extra ester linkage, which results in hydrolysis of articaine by plasma esterases. A number of studies have evaluated articaine and concluded that it is safe when used in appro­priate doses. ^* Lidocaine and articaine have the same maximal dose of 500 mg for adult patients (recommended dose, 6.6 to 7 mg/kg), but the maximum number of cartridges is different because of the differences in drug concentration (see Table 4-2 ).

* References .

Clinical Effectiveness of Articaine for Inferior Alveolar Nerve Blocks

The available literature indicates that articaine is equally effective for IAN blocks when statistically compared to other local anesthetics. ^* In comparing the anesthetic efficacy of 4% articaine with 1 : 100,000 epinephrine to 2% lidocaine with 1 : 100,000 epinephrine for IAN blocks, one study found that the two solutions were not significantly different ( Fig. 4-5 ). Two studies found no difference in efficacy between 4% arti­caine with 1 : 100,000 and 1 : 200,000 epinephrine. In summary, repeated clinical trials have failed to demonstrate any statistical superiority of articaine over lidocaine for IAN blocks.

Incidence of first mandibular molar anesthesia: comparison of 4% articaine with 1 : 100,000 epinephrine to 2% lidocaine with 1 : 100,000 epinephrine.

Results were determined by lack of response to electrical pulp testing at the maximum setting (percentage of 80 readings) across time for 60 minutes. No significant difference between the two solutions was noted.

* References .

Articaine and Uncorroborated Insurance Carrier Warning

A letter was sent to thousands of U.S. dentists in 2006 by insurer Emery and Webb/Ace USA stating, “… we have noticed an increase in reversible and, in some cases, nonreversible paresthesias (with Septocaine) … We are writing you to alert you to these events in hopes that you will not fall victim to one of these incidents.” Knowledgeable dentists and educators communicated their concerns, and a Notice of Retraction was issued:

Unfortunately, we at Emery & Webb discovered upon further review, and subsequent to the mailings, that both documents contained inaccuracies and an alarmist tone, which was not warranted … Emery and Webb has not noted an increase in malpractice claims or lawsuits in connection with articaine … It should be made clear that Emery and Webb has not conducted any scientific investigation, sampling, testing, or other investigation of the articaine anesthetic, and has no independent knowledge or data which would restrict the use of the product.

Astute clinicians should be very careful of Web chat sites and colleagues’ clinical endorsements, because they may not accurately reflect the correct information regarding articaine.

Long-Acting Anesthetics

Clinical trials with bupivacaine (Marcaine) and etidocaine (Duranest) have been conducted in patients undergoing oral surgery, endodontic treatment, and periodontic treatment. Etidocaine was withdrawn from the market by Dentsply Pharmaceuticals (York, Pennsylvania). Bupivacaine was found to have a slower onset of pulpal anesthesia than lidocaine for IAN blocks. Generally, bupivacaine provides prolonged analgesia and is indicated when postoperative pain is anticipated, but not all patients want lip numbness for an extended period. Patients should be questioned about their preference. Although bupivacaine has a somewhat slower onset than lidocaine, its duration of pulpal anesthesia in the mandible is almost twice as long (approximately 4 hours; Fig. 4-6 ).

Incidence of first mandibular molar anesthesia: comparison of 0.5% bupivacaine with 1 : 200,000 epinephrine to 2% lidocaine with 1 : 100,000 epinephrine.

Results were determined by lack of response to electrical pulp testing at the maximum setting (percentage of 80 readings) across time for 6 hours. The bupivacaine solution showed a longer duration of anesthesia than the lidocaine solution.

Ropivacaine (Naropin), a relatively new long-acting local anesthetic, is a structural homolog of bupivacaine. A number of studies have shown that ropivacaine has a lower potential for toxic CNS and cardiovascular effects than bupivacaine but produces equivalent pharmacologic effects. Ropivacaine and levobupivacaine are being developed as potentially new local anesthetics based on their stereochemistry. Both are S-isomers and are thought to cause less toxicity than the racemic mixture of bupivacaine currently marketed. A clinical trial has indicated that levobupivacaine showed significantly better postoperative pain control at 4 and 24 hours after infiltration injection than ropivacaine. Because of their decreased potential for cardiac and CNS toxicity, ropivacaine and levobupivacaine may replace bupivacaine with epinephrine in clinical dental practice.

Buffered Lidocaine

Buffering lidocaine using sodium bicarbonate raises the pH of the anesthetic solution. In medicine there is evidence that buffering lidocaine results in less pain during the injection. In dentistry, some studies found that buffered lidocaine produced less pain on injection and a faster onset of anesthesia. However, other dental studies did not find less pain on injection or a faster onset with buffered lidocaine for IAN block. Using a commercial buffering system (Onpharma, Los Gatos, California) in asymptomatic subjects, one study found a reduction in onset time and injection pain, whereas another study found no difference in these measurements. In symptomatic patients with a diagnosis of pulpal necrosis and associated acute swelling, no significant decrease in pain of infiltrations or significant decrease in pain of an incision and drainage procedure was found when the buffered anesthetic formulation was used. Most patients who had the incision and drainage procedure experienced moderate to severe pain.

Use of Mannitol

An Ohio State University research group studied the use of mannitol to increase the efficacy of nerve blocks. Mannitol, a hyperosmotic sugar solution, is thought to temporarily disrupt the protective covering (perineurium) of sensory nerves, allowing the local anesthetic to gain entry to the innermost part of the nerve. These researchers found that the use of mannitol in combination with lidocaine increased anesthetic success in IAN blocks about 15% to 20% but did not provide complete pulpal anesthesia for restorative or endodontic treatment. The drug combination may be introduced sometime in the future.

Alternative Injection Sites

Gow-Gates and Vazirani-Akinosi Techniques

Some clinicians have reported that the Gow-Gates technique has a higher success rate than the conventional IAN block injection, but controlled experimental studies have failed to show superiority of the Gow-Gates technique. Neither has the Vazirani-Akinosi technique been found superior to the standard inferior alveolar injection. In a small study of 21 patients, no difference was found between lidocaine (11 patients) and articaine (10 patients) formulations for the Gow-Gates injection in patients with irreversible pulpitis. Another study found the Gow-Gates technique had a higher success rate (52%) than the Vazirani-Akinosi technique (41%) in patients with irreversible pulpitis. Further research is indicated with both techniques in patients presenting with symptomatic irreversible pulpitis. The Vazirani-Akinosi technique is indicated for cases involving a limited mandibular opening (trismus).

Incisive Nerve Block/Infiltration at the Mental Foramen

The incisive nerve block is successful 80% to 83% of the time in anesthetizing the premolar teeth for about 20-30 minutes. It is not effective for the central and lateral incisors.

Lidocaine Infiltrations

Labial or lingual infiltration injections of a lidocaine solution alone are not effective for pulpal anesthesia in the mandible.

Articaine Infiltrations

Articaine is significantly better than lidocaine for buccal infiltration of the mandibular first molar. However, articaine alone does not predictably provide pulpal anesthesia of the first molar. There is no difference between 4% articaine with 1 : 100,000 and 1 : 200,000 epinephrine for buccal infiltration.

In anterior teeth, buccal and lingual infiltrations of articaine provide initial pulpal anesthesia, but the anesthesia declines over 60 minutes.

Attempts to Increase Success of the Inferior Alveolar Nerve Block

Increasing the Volume of Anesthetic

One possible method for increasing anesthetic success could be to double the injection volume of local anesthetic solution. However, increasing the volume of 2% lidocaine with epinephrine to 3.6 ml (two cartridges) does not increase the incidence of pulpal anesthesia with the IAN block ( Fig. 4-7 ).

Incidence of first mandibular molar anesthesia: comparison of 1.8 ml and 3.6 ml of 2% lidocaine with 1 : 100,000 epinephrine.

Results were determined by lack of response to electrical pulp testing at the maximum setting (percentage of 80 readings) across time for 60 minutes. No significant difference between the two volumes was noted.

Increasing the Epinephrine Concentration

A second approach for increasing the success of the IAN block could be to increase the concentration of epinephrine. However, when this technique was evaluated in clinically normal teeth, no advantage was seen in using a higher concentration (1 : 50,000 versus 1 : 100,000) of epinephrine.

Addition of Hyaluronidase

Hyaluronidase reduces the viscosity of the injected tissue, permitting a wider spread of injected fluids. Early studies in dentistry found that an IAN block was more easily attained and was more complete when hyaluronidase was added to an anesthetic solution. A recent study found that hyaluronidase may increase the duration of the effects of lidocaine. However, a controlled clinical trial found that adding hyaluronidase to a lidocaine solution with epinephrine did not statistically increase the incidence of pulpal anesthesia in IAN blocks. In addition, hyaluronidase increased the occurrence of adverse effects (i.e., increased pain and trismus).

Carbonated Anesthetic Solutions

Experimentally, carbonated anesthetic solutions are more effective because the anesthetic is trapped in the nerve. In addition, carbon dioxide (CO ₂ ) has a synergistic relationship with local anesthetics and a direct depressant action on nerves. However, a controlled clinical study was unable to demonstrate a superior effect of lidocaine hydrocarbonate in IAN blocks.

Diphenhydramine as a Local Anesthetic Agent

Diphenhydramine (Benadryl) has been advocated for patients who are allergic to commonly used local anesthetics. Two studies found that diphenhydramine was less effective than lidocaine for extractions. Another study found that the combinations of lidocaine/diphenhydramine with epinephrine, and diphenhydramine with epinephrine, were significantly less effective for pulpal anesthesia than lidocaine with epinephrine for IAN blocks. These researchers also found that the diphenhydra­mine solutions were more painful on injection and had a high incidence of moderate postoperative pain.

Addition of Meperidine to Lidocaine

Two studies found that the addition of meperidine (Demerol) to a lidocaine formulation did not increase the success of the IAN block.

Factors in Failure of the Inferior Alveolar Nerve Block

Accessory Innervation: Mylohyoid Nerve

The mylohyoid nerve is the accessory nerve most often cited as a cause of failure of mandibular anesthesia. A controlled clinical trial compared the IAN block alone to a combination of the IAN block and a mylohyoid nerve block using 2% lidocaine with 1 : 100,000 epinephrine ( Fig. 4-8 ), which was aided by the use of a peripheral nerve stimulator. The investigators found that the mylohyoid injection did not significantly enhance pulpal anesthesia of the IAN block ( Fig. 4-9 ), so the study does not support the hypothesis that the mylohyoid nerve is a major factor in failure of the IAN block.

Injection site for the mylohyoid nerve block.

Incidence of first mandibular molar anesthesia: comparison of the combination mylohyoid infiltration plus the inferior alveolar nerve block to the inferior alveolar nerve block alone.

Results were determined by lack of response to electrical pulp testing at the maximum setting (percentage of 80 readings) across time for 60 minutes. No significant difference between the two techniques was noted.

Accuracy of Injection

It has been theorized that an inaccurate injection contributes to inadequate mandibular anesthesia, but a number of studies determined that the use of ultrasound, a peripheral nerve stimulator, or radiographs to guide needle placement for IAN blocks did not result in more successful pulpal anesthesia. The authors of these studies speculated that the anesthetic solution migrated along the path of least resistance, which was determined by fascial planes and structures encountered in the pterygomandibular space. These studies highlight an important clinical point: Lack of pulpal anesthesia is not necessarily the result of an inaccurate injection.

Needle Deflection

Needle deflection has been proposed as a cause of failure with the IAN block. Several in vitro studies have shown that beveled needles tend to deflect toward the nonbeveled side (i.e., away from the bevel). ^* To compensate for this, a bidirectional needle rotation technique using the computer-controlled local anesthetic delivery system (CCLAD) (Milestone Scientific, Livingston, New Jersey) has been proposed in which the CCLAD handpiece assembly and needle are rotated in a fashion similar to the rotation of an endodontic hand file. The technique was found to reduce deflection during insertion of the needle. A controlled clinical trial compared the anesthetic success of the conventional IAN block using two needle insertion methods. However, no significant difference in anesthetic success was seen when the needle bevel was oriented away from the mandibular ramus (so that the needle would deflect toward the mandibular foramen [50% success]) compared with the bidirectional CCLAD needle rotation technique (56% success). Neither technique resulted in an acceptable rate of anesthetic success in patients with symptomatic irreversible pulpitis.

* References .

Needle Bevel and Success

In asymptomatic subjects, the orientation of the needle bevel away or toward the mandibular ramus for an IAN block did not affect anesthetic success or failure. Therefore, the use of commercial needles with markers to indicate the needle bevel is not necessary.

Speed of Injection and Success

A slow inferior alveolar nerve block increases success over a fast injection but not for patients diagnosed with irreversible pulpitis.

Cross-Innervation

Cross-innervation from the contralateral inferior alveolar nerve has been implicated in failure to achieve anesthesia in anterior teeth after an IAN injection. Experimentally, cross-innervation occurs in incisors but plays a very small role in failure of an IAN block.

Red Hair

In medicine, red-haired females have shown reduced subcutaneous efficacy of lidocaine and increased requirements for desflurane. However, in dentistry, having red hair was unrelated to success rates of the inferior alveolar nerve block, although it has been shown to be associated with higher levels of dental anxiety.

A Theory on Why Failure Occurs with the Inferior Alveolar Nerve Block in Restorative Dentistry

The central core theory may be the best explanation of why failure occurs with the IAN block. According to this theory, nerves on the outside of the nerve bundle supply molar teeth, and nerves on the inside of the nerve bundle supply anterior teeth ( Fig. 4-10 ). Even if deposited at the correct site, the anesthetic solution may not diffuse into the nerve trunk and reach all nerves to produce an adequate block. Although this theory may explain the higher experimental failure rates with the IAN block in anterior teeth compared with posterior teeth, ^* it does not explain the increased failure rate observed in painful teeth.

Central core theory.

The axons in the mantle bundle supply the molar teeth, and those in the core bundle supply the anterior teeth. The extraneural local anesthetic solution diffuses from the mantle to the core.

(Modified and redrawn from De Jong RH: Local anesthetics, St Louis, 1994, Mosby.)

* References .

Enhancement of Mandibular Anesthesia for Restorative Dentistry

Supplemental Articaine Infiltrations

An important clinical finding is that an articaine infiltration of the first molar, premolars, and anterior teeth after an IAN block should provide pulpal anesthesia for approximately 1 hour. The second molar may require a supplemental intraosseous (IO) or intraligamentary (IL) injection to achieve success.

Supplemental Intraosseous Anesthesia

Supplemental IO injections of lidocaine and mepivacaine with vasoconstrictors allow quick onset and increase the success of the inferior alveolar nerve block for approximately 60 minutes ( Fig. 4-11 ). The addition of a supplemental IO injection reduced the incidence of slow onset of pulpal anesthesia to zero compared with the IAN block alone (18% incidence). Using 3% mepivacaine plain for IO injection results in pulpal anesthesia for approximately 30 minutes ( Fig. 4-12 ).

Incidence of first mandibular molar anesthesia: comparison of the combination intraosseous injection of 2% lidocaine with 1 : 100,000 epinephrine plus the inferior alveolar nerve block to the inferior alveolar nerve block alone.

Results were determined by lack of response to electrical pulp testing at the maximum setting (percentage of 80 readings) across time for 60 minutes. The combination technique was significantly better at all postinjection times.

Incidence of first mandibular molar anesthesia: comparison of the combination intraosseous injection with 3% mepivacaine plus the inferior alveolar nerve block to the inferior alveolar nerve block alone.

Results were determined by lack of response to electrical pulp testing at the maximum setting (percentage of 80 readings) across time for 60 minutes. The combination technique proved significantly better for approximately 30 minutes.

Supplemental Intraligamentary Anesthesia

Supplemental IL injections of 2% lidocaine with 1 : 100,000 epinephrine increase the success of the inferior alveolar nerve block, but the duration is approximately 23 minutes.

Maxillary Anesthesia for Restorative Dentistry

Descriptions of conventional techniques for maxillary anes­thesia are available for review in numerous articles and textbooks.

2% Lidocaine with 1 : 100,000 Epinephrine

As a frame of reference, the most commonly used injection for anesthetization of maxillary teeth is infiltration with a cartridge of 2% lidocaine with 1 : 100,000 epinephrine.

Anesthetic Success

Infiltration results in a fairly high incidence of successful pulpal anesthesia (around 87% to 92%). ^* However, some patients may not be anesthetized because of individual variations in response to the drug administered, operator differences, and variations of anatomy and tooth position.

* References .

Onset of Pulpal Anesthesia

Pulpal anesthesia usually occurs in 3 to 5 minutes. ^†

† References .

Duration of Pulpal Anesthesia

The duration of pulpal anesthesia is a problem with maxillary infiltrations. ^‡ Pulpal anesthesia of the anterior teeth declines after about 30 minutes, with most losing anesthesia by 60 minutes. ^§ In premolars and first molars, pulpal anesthesia is good until about 40-45 minutes and then it starts to decline. ^‖ Additional local anesthetic should be administered depending on the duration of the procedure and the tooth group affected.

‡ References .

§ References .

‖ References .

Time Course of Pulpal Anesthesia for the Maxillary First Molar

Figure 4-13 shows the time course for complete pulpal anesthesia for an asymptomatic first molar, as defined by the percentage of patients who do not respond at all to an EPT stimulus over time. Some patients had a slow onset of anesthesia until around 11 minutes. The overall success rate (no response at the device’s highest setting) is 95% to 100%, with peak effects observed at around 30 minutes after injection.

Incidence of first maxillary molar anesthesia, as determined by lack of response to electrical pulp testing at the maximum setting (percentage of 80 readings) across time for 60 minutes.

Significance of Lip Numbness

Soft tissue anesthesia (lip or cheek numbness) is not necessarily related to the duration of pulpal anesthesia. Pulpal anesthesia does not last as long as soft tissue anesthesia.

Alternative Anesthetic Solutions for Infiltrations

Plain Solutions: 3% Mepivacaine (Carbocaine, Polocaine, Scandonest) and 4% Prilocaine (Citanest Plain)

Anesthesia duration is shorter with these solutions. Therefore, use these for procedures of short duration (10 to 15 minutes) ( Fig. 4-14 ). These agents are generally not as safe as solutions with vasoconstrictors if large volumes are administered because they are rapidly absorbed systemically, resulting in excessive plasma concentrations and possible toxic reactions.

Incidence of first maxillary molar anesthesia: comparison of 3% mepivacaine to 2% lidocaine with 1 : 100,000 epinephrine.

Results were determined by lack of response to electrical pulp testing at the maximum setting (percentage of 80 readings) across time for 60 minutes. The 3% mepivacaine showed a shorter duration of anesthesia than the lidocaine solution.

4% Prilocaine with 1 : 200,000 Epinephrine (Citanest Forte), 2% Mepivacaine with 1 : 20,000 Levonordefrin (Carbocaine with Neo-Cobefrin), and 4% Articaine with 1 : 100,000 Epinephrine (Septocaine, Articadent, Zorcaine)

These formulations are similar to 2% lidocaine with 1 : 100,000 epinephrine.

0.5% Bupivacaine with Epinephrine (Marcaine)

Success rates (no response to EPT) with bupivacaine range from 80% to 95% in the maxillary lateral incisor, compared with 50% in the maxillary second premolars. Although bupivacaine provides long-term anesthesia with the IAN block, it does not provide prolonged pulpal anesthesia with maxillary infiltration injection. In the lateral incisor, bupivacaine has a shorter duration of pulpal anesthesia than lidocaine. In the first molar, bupivacaine’s duration of pulpal anesthesia is equivalent to that of lidocaine. Neither agent provides pulpal anesthesia for an hour.

Extending the Duration of Pulpal Anesthesia for Maxillary Teeth

Increasing the Solution Volume

A two-cartridge volume of 2% lidocaine with epinephrine extends the duration of pulpal anesthesia but not for 60 minutes.

Increasing the Epinephrine Concentration

Increasing the epinephrine concentration to 1 : 50,000 epinephrine increases duration for the lateral incisor but not the first molar. Duration was not 60 minutes in either teeth.

Repeating the Infiltration

Adding another cartridge of 2% lidocaine with epinephrine at 30 minutes in anterior teeth and 45 minutes in posterior teeth significantly improves the duration of pulpal anesthesia and may be the best way to extend the duration of pulpal anesthesia ( Fig. 4-15 ).

Incidence of maxillary lateral incisor pulpal anesthesia using an initial infiltration and a repeated infiltration 30 minutes later (both infiltrations used 1.8 ml of 2% lidocaine with 1 : 100,000 epinephrine).

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