Local Anesthetic Usage Among Dentists: German and International Data

Abstract

The aim of this study was to analyze the use of dental local anesthetics in Germany compared with international data. The type and distribution of dental local anesthetics and added vasoconstrictors based on a representative sample of German dentists itemized over a period of 7 years (2011 to 2017) were evaluated and statistically analyzed. The results were compared with international dental local anesthetic consumption data published since 2005. With a consistent market share of nearly 98%, articaine was the first-line local dental anesthetic agent in Germany. During the investigation period, German dental local anesthetics with epinephrine 1:200,000 had ∼50% market shares, whereas formulations with epinephrine 1:100,000 had 40% to 45% market shares. Articaine, with market shares between 38% and 81%, was also the preferred anesthetic agent in various other countries, with the notable exceptions of the United Kingdom and the United States, where lidocaine was the preferred local anesthetic agent. Epinephrine was the preferred vasoconstrictor internationally, similar to Germany. The larger market share of higher concentrated epinephrine 1:100,000 was remarkable, considering the increasing number of medically compromised patients. Increased consideration for using agents with reduced dosages of epinephrine (1:200,000) is generally recommended.

Local anesthetics in combination with vasoconstrictors comprise the foundation of pain control in dentistry and oral and maxillofacial surgery and provide ample benefits for the patient and the clinician. However, patients may experience dental fear and anxiety for a variety of reasons, including the use of local anesthesia. In a recent clinical study, 26 of 100 patients undergoing oral surgery reported being afraid of pain during and after the procedure as well as fearing the local anesthetic injection.¹ Therefore, achieving optimal intra- and postoperative pain control with the use of local anesthesia is essential for satisfactory patient cooperation. Malamed² characterized local anesthetics as the most important drugs in dentistry because of their omnipresent use. It has been estimated that more than 300 million local anesthetic cartridges are used annually by dentists in the United States.² Local anesthetic agents used in medicine and dentistry primarily function by impairing afferent neuronal conduction and can be categorized into 2 classes based on their molecular structure: amides (lidocaine, bupivacaine, prilocaine, ropivacaine, articaine, mepivacaine) and esters (benzocaine, cocaine, procaine, tetracaine).

Local anesthetics are considered relatively safe; however, given the high number of injections that are administered, adverse reactions are inevitable.³ While adverse effects may be localized or systemic in nature, they tend to be infrequent, with serious complications being exceedingly rare.^4,5 In 181,325 cases of maxillofacial operations in which a local anesthetic was used, only 1222 complications occurred, of which 97% were diagnosed as vasovagal syncope and only 2 cases were reported as cerebrovascular accidents.⁶

To take advantage of the benefits of different local anesthetic and vasoconstrictor options, one must be familiar with their pharmacotherapeutic characteristics. In the light of an increasing number of at-risk patients with multiple medical comorbidities,⁷ dentists would be well advised to adjust their anesthetic treatment accordingly. As such, the purpose of this study is to examine the various types and market shares of local anesthetics and vasoconstrictors used by dental practitioners in Germany over a period of 7 years and compare these data with available international data.

METHODS

The German data for this study was obtained from the Deutscher Dentalmarktbericht (DDM), which is published twice a year by Gesellschaft für Konsumforschung (Nuremberg, Germany), the largest German market research company. The DDM is a projected sales report based on a sample of 770 dentists, 60 orthodontists, 50 oral surgeons, and 40 maxillofacial surgeons. The data are based on membership statistics of the regional chambers of dentists (ie, the Landeszahnärztekammern). The sample is extrapolated by validated statistical methods to Germany as a whole and therefore is thought to represent the field of dental health care in Germany. Market share data from 2011 to 2017 were obtained from the DDM for this sample group, demonstrating what agents were purchased, as evident by recorded invoices for the various dental local anesthetics.

International data were identified and obtained using a literature search for consumption data on dental local anesthetics in different countries. Studies from the scientific literature regarding statistical data on local anesthetic use in dentistry since 2005 were reviewed using PubMed and Medline databases. The search included 1 or a combination of the following keywords, in singular or plural: administration, anaesthesia, anaesthetic, anesthetic, articaine, carticaine, comparison, data, dental, dentist, epinephrine, lidocaine, local, mepivacaine, prilocaine, statistic, and vasoconstrictor. Search results were evaluated for relevance, and original publications were obtained. The reference lists were reviewed to obtain additional information regarding statistics on local anesthetic and vasoconstrictor use by dentists.

In some publications, the authors focused on the use of specific local anesthetics in various kinds of medically compromised patients in comparison with healthy patients. In such publications, only the data relating to healthy patients were included.^8–10

Statistical Analysis

Analysis of the German data was based on the relative market shares per year for local anesthetic agents irrespective of any added vasoconstrictors sold to German dentists from 2011 to 2017. Because of the small sample sizes, a nonparametric statistical test was applied. Friedman's test was used to determine whether there were any statistically significant differences between the rank-ordering of market shares of the various anesthetic agents and vasoconstrictors at the different years of investigation. Pearson correlation coefficient was used to measure the correlation between the market shares of the anesthetic agents and vasoconstrictors.

Statistical tests were performed with IBM SPSS Statistics 24.0 software for Windows (SPPS Inc, Chicago, Ill) and were considered significant if p < .05.

RESULTS

By Friedman's test, we found a statistically significant different ranking within the groups of the local anesthetics and the vasoconstrictors during the investigation period (p < .05; Tables 1 and 2).

Table 1.

Test Statistics (Friedman Test) for Local Anesthetics (p < .05)

n	7
Chi-square	19,348
df	3
Asymptomatic significance	.000

Table 2.

Test Statistics (Friedman Test) for Vasoconstrictors (p < .05)

n	7
Chi-square	26,857
df	4
Asymptomatic significance	.000

German Market Share Data for Dental Local Anesthetic Agents

Articaine was by far the most commonly purchased dental local anesthetic agent in Germany with a relative market share that increased slightly from 97.2% in 2011 to 98.1% in 2017 (Figure 1). During that same time period, mepivacaine, lidocaine, and prilocaine made up the remaining market share in descending order. The increased market share for articaine from 2011 to 2017 correlated significantly with the decrease in market share for lidocaine (r = −.851, p = .015). The market shares of mepivacaine remained stable at 1.4% over the investigation period, whereas lidocaine slightly decreased from 0.8% in 2011 to 0.5% in 2017. The proportion of prilocaine fell from 0.6% in 2011 to 0% in 2017. This course can be explained by the fact that until 2016 in Germany, prilocaine was offered in combination with felypressin. Since 2017, cartridges with prilocaine and felypressin are no longer available on the dental market. In Germany, bupivacaine is also not offered to dental practitioners.

Figure 1.

Market shares of the different dental local anesthetics in Germany (2011–2017).

German Market Share Data for Vasoconstrictors

Epinephrine was the vasoconstrictor of choice in Germany, with market shares approximating 95% or more during the investigation period. Among the different concentrations of epinephrine offered by the dental industry for anesthetic injections (1:50,000 in combination with lidocaine, 1:100,000 in combination with articaine or lidocaine, 1:200,000 in combination with articaine, 1:400,000 in combination with articaine, and plain articaine or mepivacaine), the 1:200,000 concentration was the preferred option in Germany (2017 market share of 50.8%). The second most purchased concentration was 1:100,000, with relative proportions between 40.4% in 2013 and 45.6% in 2015 (Figure 2). The shares of epinephrine 1:100,000 and epinephrine 1:200,000 had a significant negative correlation (r = −.948, p = .001). The market shares of epinephrine 1:50,000 and1:400,000 as well as felypressin all taken together accounted in no year for more than 3.4%. Only about 3% of all dental anesthetics purchased in Germany are free of vasoconstrictors (Figure 2).

Figure 2.

Market shares of the different vasoconstrictors in Germany (2011–2017).

International Local Anesthetic Data

In total, we found only 6 international scientific publications since 2005 that included percentage ratios on the use or consumption of different local anesthetics for dentistry in individual countries or regions (Figure 3). Five of these studies were based on self-reported retrospective surveys of dentists.^8–13 Only the data for the United States, quoted by Malamed in 2006 his clinical update,² represented market shares provided by a big pharmaceutical producer of local anesthetics (Septodont, Inc, Lancaster, Penn).

Figure 3.

Reported usage/market shares of the different dental local anesthetics in international studies.

Aside from the United States and the United Kingdom, the data demonstrated that articaine was the most popular local anesthetic agent for dentistry and lidocaine was second (Figure 3).^9,10,12,13 Notably, articaine's popularity was greater in Germany than it was in any other country included in this study (Australia, Bulgaria, Canada, France, United Kingdom, and United States). In the United States and the United Kingdom, lidocaine was the most frequently purchased or used dental local anesthetic and articaine was second.^2,8 With the exceptions of Bulgaria and the United States, the percentage shares of mepivacaine were <10%.^2,9 Prilocaine was the least popular dental local anesthetic in all of the countries included in this study.

International Vasoconstrictor Data

Vasoconstrictor data from different countries were rare and mostly incomplete. Only 3 of the surveys mentioned above provided data on the usage of different vasoconstrictors by dental practitioners.^8,10,11 Similar to Germany, formulations with epinephrine were the most commonly used (Figure 4). The range extended from 82.6% in France to 96% in Germany. Detailed data identifying specific vasoconstrictor agents and concentrations along with local anesthetic agents were available only in the survey by Gaffen and Haas,¹¹ which reported local anesthetic formulations used in Ontario. In contrast to the data in our study (Figure 2), the formulations with the higher-concentrated epinephrine 1:100,000 were the most widely used (56%), followed by those containing epinephrine 1:200,000 (30.8%).¹¹ The findings of the French and Canadian surveys revealed that dentists in these countries seldom chose plain local anesthetics; only in Canada, the estimated use of vasoconstrictor-free formulations accounted for nearly one-tenth of all anesthetic formulations.^10,11 Other vasoconstrictors, such as norepinephrine or levonordefrin, generally were of minor importance, but in France only, the proportion was greater than 10%.¹⁰

Figure 4.

Reported usage/market shares of the different vasoconstrictors in international studies.

DISCUSSION

Both in Germany and internationally, the dental market offers a large variety of different local anesthetic agents with and without vasoconstrictors from which the dental practitioner can choose. But there is little information on the types and market shares of local anesthetics used by dentists throughout the world. The reasons for this problem are various. In most countries, there is no oversight by regulatory bodies regarding the overall frequency with which local anesthetics are used in dental treatment. As a result, accurate data on the relative use of various anesthetic formulations available in dental cartridges are not publicly available, primarily because these cartridges are distributed to dentists by dental supply companies in most countries. Reportedly, pharmaceutical and dental supply companies often reject requests to share such data as they have no legal obligation to do so and often decline on the grounds of “commercial confidentiality.”¹³

Dental Local Anesthetics

In Germany, articaine has occupied a dominant position on the market for decades.⁴ This drug received approval in Germany in 1976. In 1984, it was released in Canada, followed by the United Kingdom in 1998, the rest of Europe and the United States in 2000, and Australia in 2005.¹³ The amide structure of articaine is similar to that of other commonly used amide local anesthetics; however, its unique molecular characteristics include a thiophene ring and an ester group, which allows greater lipid solubility and potency to diffuse across neuronal membranes, which makes articaine's metabolism unique.^5,14 Articaine's amide linkage undergoes slow hepatic biotransformation, which is responsible for ∼10% of its metabolism, while ∼90% is hydrolyzed quickly via nonspecific plasma esterases into its inactive metabolite articainic acid.^14–16 The short elimination half-time approximating 20 minutes produces a wide therapeutic range and low systemic toxicity.^15,16 In healthy elderly and young volunteers, it has been shown that articaine metabolism is age independent.¹⁷ In contrast to articaine, lidocaine has active metabolites and an elimination half-life of about 100 minutes.⁵ Patients with congestive heart failure and hepatic disease can have pronounced changes in lidocaine metabolism and clearance because of its extensive hepatic metabolism and clearance, which depend heavily on hepatic blood flow.¹⁸

Several studies and reviews have assessed the efficacy of articaine versus lidocaine for pulpal anesthesia in children or with mandibular infiltration techniques and suggest that articaine achieves anesthetic success superior to that of lidocaine.^19–21 The conclusion of an umbrella review by Badr and Aps,²² which covered the past 10 years, was that none of the dental local anesthetic amides provide 100% success, particularly in the mandible. Nevertheless, among the amides used in dental local anesthesia articaine has been heavily researched and shows the highest efficacy of the amides used in dental local anesthesia.^19–22 Therefore, it is not surprising that articaine holds high market shares in several countries in addition to Germany, including Australia, Bulgaria, Canada, and France.^9,10,12 However, in the United States and the United Kingdom, lidocaine continues to dominate the market (Figure 3).^2,8

A controversial issue is the higher potential neurotoxicity of articaine compared with lidocaine or prilocaine.^23–26 In a current systematic review, the included articles present no conclusive evidence to suggest that higher-concentrated 4% articaine causes more nerve damage than 2% lidocaine.²⁶ Furthermore, in an in vitro study, articaine failed to damage neural cells more than lidocaine.²⁷ Interestingly, in a randomized double-blind study, lowering the concentration of articaine from 4% to 2% did not affect the onset of action, the local anesthetic effect, or the postoperative complications. However, the duration of soft-tissue anesthesia was shortened by nearly half an hour, which was statistically significant.²⁸ In addition to articaine, prilocaine is also solely available in dental cartridges as a 4% solution, the highest concentration among injectable dental local anesthetics. In a retrospective review of voluntary reports of nonsurgical paresthesias, the observed frequencies of paresthesias for prilocaine and articaine were significantly greater than expected.²⁴ The lingual nerve was affected more often than the inferior alveolar nerve. Pogrel²³ found a higher incidence of nerve damage caused by prilocaine when compared with its relative market share, whereas in other studies, more nerve injuries were associated with articaine.²⁵ One aspect of this phenomenon may be articaine's increasing usage over the years compared with lidocaine or prilocaine.¹¹ These data suggest that dental practitioners should be careful when choosing to use 4% articaine for inferior alveolar nerve blocks until further scientific research has been performed.^24–26

Internationally, prilocaine and mepivacaine are considerably less popular dental local anesthetic agents (Figure 3). In contrast to lidocaine and articaine, mepivacaine possesses little to no vasodilating property.⁵ Hence, mepivacaine is still the local anesthetic of choice for patients with absolute contradictions for vasoconstrictors.⁴ In patients with potential allergic reactions, dentists should use plain anesthetics because they are free of sulfite-containing antioxidants.⁵ Prilocaine may induce clinically symptomatic methemoglobinemia and should not be used in children younger than 6 months of age, in pregnant women, or in patients taking other oxidizing drugs.⁵

Vasoconstrictors

In 2017, anesthetic solutions with epinephrine dominated ∼96% of the German market (Figure 2). Similar to Germany, epinephrine was the most frequent vasoconstrictive agent used internationally (Figure 4). Despite the popularity of epinephrine 1:100,000 in Canada¹¹ and in Germany (Figure 2), data have shown that the higher-concentrated vasoconstrictors do not provide improved onset or duration for mandibular nerve blocks⁵ or reduce local anesthetic serum concentrations.²⁹ It has been shown that increased concentrations of epinephrine are associated with increased sympathomimetic side effects primarily affecting the cardiovascular system.^3–5,29,30 Even small doses of epinephrine can provoke cardiovascular effects (ie, increased heart rate and blood pressure).^5,29,30 Moreover, beside their potential side effects, vasoconstrictors can be problematic because of potential adverse drug interactions such as with tricyclic antidepressants.³¹ As a consequence, the use of epinephrine-reduced or plain solutions may be prudent.^4,5,8,30 However, in Germany, as in other countries, solutions without vasoconstrictors are likely used very rarely in dentistry, as evident by the analyzed data demonstrating market shares less than 10% (Figures 2 and 4). Perhaps the increasing importance of operative dentistry (eg, periodontology, oral surgery, implantology) with the need for an excellent visualization of the surgical field and less bleeding might explain the widespread use of epinephrine 1:100,000 in Canada or in Germany (Figure 2).^5,32

The frequent use of higher-concentrated epinephrine, as found in Germany or Canada, may indicate that the awareness of dental practitioners to adapt their selection of different vasoconstrictors to the risk profile of the individual patient could be improved, particularly considering the growing number of medically compromised patients. The statement of Daubländer and coworkers,⁴ that a differentiated local anesthesia that is well adjusted to the patient's specific requirements (type and duration of dental intervention, risk factors) is not yet applied in the daily dental routine, is as true today as it was more than 20 years ago.

Limitations

This study was based on retrospective data generated by a limited number of participants. Details concerning gender, age, or specialization of the participants were not disclosed to the authors. In contrast to questionnaires, purchase data were not influenced by distortions of memory (recall bias) or a reduced willingness to answer or participate (nonresponse bias). However, neither the market share nor questionnaire data were able to capture actual usage of different local anesthetics and vasoconstrictors. The international studies were somewhat dated; however, this reflected a lack of research in this area. Unfortunately, the authors could not receive further consumption data from generally accessible sources. Data on other local anesthetic agents, such as bupivacaine, could not be included as they are not available on the German dental market.

CONCLUSION

In this study, we demonstrated that in most of the analyzed countries, articaine was more frequently administered than lidocaine for dentistry. Other local anesthetics such as mepivacaine or prilocaine were generally available but were not used frequently. On the worldwide market epinephrine has prevailed over felypressin and other vasoconstrictors as the absolute most common vasoconstrictor used in combination with local anesthetics for dentistry. In view of the growing number of patients with underlying cardiovascular risks in an aging society, epinephrine-reduced or vasoconstrictor-free local anesthetic solutions should be considered more frequently.