Filing 4

ENTRY Dismissing Complaint and Directing Further Proceedings - The request to proceed in forma pauperis [dkt. 2 ] is granted. Mr. Noll's complaint must be dismissed for the reason set forth above. Nothing in this action prevents Mr. Noll fro m filing a malpractice action in state court. Mr. Noll shall have through February 23, 2017, in which to show cause why Judgment consistent with this Entry should not issue. (See Entry.) Copy to Plaintiff via U.S. Mail. Signed by Judge Tanya Walton Pratt on 1/24/2017. (Attachments: # 1 Article)(JLS)

Download PDF
C O V E R S T O R Y Occurrence of paresthesia after dental local anesthetic administration in the United States Gabriella A. Garisto, DDS; Andrew S. Gaffen, DDS; Herenia P. Lawrence, DDS, MSc, PhD; Howard C. Tenenbaum, DDS, PhD; Daniel A. Haas, DDS, PhD A J ✷ D A ✷ ® I A T IO N Background. Several studies have suggested that the likelihood of paresthesia may depend on the local anesthetic used. The purpose of this study N C A UING EDU 1 was to determine if the type of local anesthetic RT ICLE administered had any effect on reports of paresthesia in dentistry in the United States. Methods. The authors obtained reports of paresthesia involving dental local anesthetics during the period from November 1997 through August 2008 from the U.S. Food and Drug Administration Adverse Event Reporting System. They used χ2 analysis to compare expected frequencies, on the basis of U.S. local anesthetic sales data, with observed reports of oral paresthesia. Results. During the study period, 248 cases of paresthesia occurring after dental procedures were reported. Most cases (94.5 percent) involved mandibular nerve block. The lingual nerve was affected in 89.0 percent of cases. Reports involving 4 percent prilocaine and 4 percent articaine were 7.3 and 3.6 times, respectively, greater than expected (χ2, P < .0001) on the basis of local anesthetic use by U.S. dentists. Conclusions. These data suggest that paresthesia occurs more commonly after use of 4 percent local anesthetic formulations. These findings are consistent with those reported in a number of studies from other countries. Clinical Implications. Until further research indicates otherwise, dentists should consider these results when assessing the risks and benefits of using 4 percent local anesthetics for mandibular block anesthesia. Key Words. Paresthesia; local anesthetics; prilocaine; articaine; inferior alveolar nerve block; mandibular nerve block. JADA 2010;141(7):836-844. T A ABSTRACT CON lthough local anesthetics are safe, effective and essential drugs for dentistry, their use may involve complications. One such potential outcome is paresthesia, which refers to a neuropathy that manifests as persistent anesthesia or an altered sensation ranging from complete numbness to burning, tingling or continual pain.1-3 Most oral paresthesias are caused by direct trauma associated with a surgical procedure, such as a dental extraction or orthognathic surgery. However, studies have shown that paresthesia also can occur after nonsurgical dentistry.4-9 The exact cause of this is not known, but it may be one or a combination of several factors: traumatic injury to the nerve via direct contact with the needle, hemorrhage into the nerve sheath, hydrostatic pressure from the injection or potential neurotoxicity from the local anesthetic itself.2 The hypothesis that local anesthetics may be neurotoxic is controversial.10,11 An initial report with results suggesting this possibility was a retrospective examination of nonsurgical paresthesia in Ontario, Dr. Garisto is a master’s/specialty student in graduate dental anaesthesia, Faculty of Dentistry, University of Toronto. Dr. Gaffen is a master’s/specialty student in graduate endodontics, Faculty of Dentistry, University of Toronto. Dr. Lawrence is an associate professor, Discipline of Dental Public Health, Faculty of Dentistry, University of Toronto. Dr. Tenenbaum is a professor, Discipline of Periodontology, Faculty of Dentistry, University of Toronto. Dr. Haas is the Chapman Chair, an associate dean, a professor and the head, Discipline of Dental Anaesthesia, Faculty of Dentistry, University of Toronto, 124 Edward St., Toronto, Ontario M5G 1G6, Canada, e-mail “”. Address reprint requests to Dr. Haas. 836 JADA, Vol. 141 July 2010 Copyright © 2010 American Dental Association. All rights reserved. Reprinted by permission. C Canada, from 1973 through 1993.4 Investigators in that study found an overall incidence of paresthesia to be 1:785,000, with the two drugs most often implicated being 4 percent prilocaine and 4 percent articaine. The number of annual cases of paresthesia increased beginning in 1985, shortly after the introduction of articaine into the Canadian market. Results from that study also showed that the lingual nerve was affected in 64 percent of all reported cases. Results from a follow-up study in which researchers investigated reports from 1994 through 1998 found, once again, that paresthesia most often was associated with 4 percent prilocaine and 4 percent articaine and that the lingual nerve was involved in 70 percent of the cases.5 More recently, an analogous study of nonsurgical paresthesia in Ontario during the period from 1999 through 2008 yielded similar results; as before, 4 percent prilocaine and 4 percent articaine were associated more frequently with neuropathy than were any of the other local anesthetics available in dental cartridges.12 Also as before, the lingual nerve was affected most frequently, being involved 79.1 percent of the time. Thus, all three studies from Ontario had consistent findings. The results of a study conducted in northern California before the release of articaine in the United States showed that 4 percent prilocaine was reported more often than other local anesthetics with respect to permanent paresthesia after local anesthetic administration.6 Results of another study conducted in northern California showed that there were more reports of 4 percent prilocaine’s being associated with paresthesia, and reports of 4 percent articaine’s association and 2 percent lidocaine’s association were proportional to and lower than, respectively, those predicted on the basis of their estimated use.13 In Denmark, investigators found that 88 percent of reports of nerve injuries involved articaine.8 Results of another study conducted in Denmark showed an increase in cases of paresthesia after the market introduction of 4 percent articaine and that the lingual nerve was affected in 78 percent of cases.9 To summarize, reported studies of paresthesia have been conducted in Ontario, Canada; Denmark; and northern California. Yet, no comparable assessment has been done in the United States as a whole. Therefore, our purpose in this study was to determine if the type of local anesthetic administered had any effect on reports of paresthesia in O V E R S T O dentistry in this country. We accomplished this by retrospectively analyzing cases of nonsurgical paresthesia associated with dental local anesthetics that were voluntarily reported to the U.S. Food and Drug Administration (FDA) from November 1997 through August 2008. METHODS We obtained ethics approval for this study from the University of Toronto Health Sciences Research Ethics Board. We obtained voluntarily submitted adverse event reports involving the dental local anesthetics currently available in the United States—namely, articaine, bupivacaine, lidocaine, mepivacaine and prilocaine—from the FDA’s Adverse Event Reporting System (AERS). The AERS is a computerized information database designed to support the FDA’s postmarketing safety surveillance program for all approved drug and therapeutic biological products. The FDA began entering adverse event reports into the AERS on Nov. 1, 1997. The system relies on voluntary reports submitted by health care professionals, consumers or others who become aware of a possible drug-related adverse event. This information is available to the public at large through the Freedom of Information Act.14 We examined all reports during this period that denoted a neuropathy, including paresthesia, hyperesthesia, hypoesthesia, dysesthesia, dysgeusia, ageusia and a burning sensation. Inclusion criteria were all of the following three items: an oral paresthesia; a dental procedure; a case in the United States. Exclusion criteria included any one of the following: a surgical procedure such as extraction, implant placement or periodontal surgery, because such procedures can cause paresthesia; use of an intraosseous device, which can traumatize the nerve directly; a local anesthetic such as etidocaine that is no longer available in dental cartridges in the United States; or a case report obtained only from the scientific literature. We extracted the following case parameters and subjected them to descriptive statistical analysis by using software (SPSS, version 17, SPSS, Chicago): the local anesthetic’s generic name; the year in which the adverse event occurred; the age and sex of the patient; the route ABBREVIATION KEY. AERS: Adverse Event Reporting System. FDA: Food and Drug Administration. JADA, Vol. 141 Copyright © 2010 American Dental Association. All rights reserved. Reprinted by permission. July 2010 837 R Y O V E R S T O R Y reported to the FDA’s AERS for the five local anesthetics 30 of interest. The FDA provides line listings 25 that summarize the information about Articaine 20 individual adverse Bupivacaine Lidocaine events. Actual hardMepivacaine Prilocaine 15 copy reports conMultiple taining further 10 details can be obtained on request. 5 Our review of each of these listings pro0 vided information 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 that warranted YEAR requesting 533 Figure 1. Reported number of cases of nonsurgical paresthesia, according to year and local anesthetic drug. detailed reports. Further analysis of of drug administration; dental arch; side; specific these 533 reports revealed that 248 of them satisanatomic structures affected (to allow us to deterfied our inclusion and exclusion criteria. In addimine which branch of the trigeminal nerve was tion to these 248, there were 19 cases involving involved); injection-associated events, such as dental care in which surgery was specified, one of pain, electric shock or positive aspiration of blood; which involved the use of multiple agents. In 89 any additional symptoms; the dental procedure of the 248 cases, nonsurgical dentistry was speciinvolved; multiple drugs injected; vasoconstrictor fied. For the 159 of the 248 cases for which no use; and resolution of the adverse event. procedure was listed, we assumed that they We obtained data regarding the sales of dental involved nonsurgical dentistry. Single agents local anesthetic cartridges in the United States, were used in 226 of the 248 cases, and 22 involved yearly from 1997 through 2008, from a research the use of multiple drugs, all of which included company (Strategic Data Marketing, Rochelle either prilocaine or articaine. In reports involving Park, N.J., unpublished data, 2009). only one drug, a total of 116 (51.3 percent) cases We used statistical analysis to test the null involved 4 percent articaine, 97 (42.9 percent) hypothesis that each local anesthetic had no involved 4 percent prilocaine, 11 (4.9 percent) effect on the frequency of reporting of cases of involved 2 percent lidocaine, one (0.4 percent) dental paresthesia. We used the χ2 test to cominvolved 0.5 percent bupivacaine and one pare the expected frequencies of oral paresthesia, (0.4 percent) involved 3 percent mepivacaine. We on the basis of sales data, with observed reports excluded one case in which an intraosseous injecof such paresthesia made to the AERS. When the tion (Stabident, Fairfax Dental, Miami) was used, expected frequency in any one group was less as it may directly traumatize the nerve. than five, we considered χ2 to be less reliable, so Figure 1 shows the observed cases of pareswe used the exact binomial probability distributhesia per local anesthetic drug according to year. tion instead to compare outcomes. All statistical Data for 1997 represent only two months because tests were two-tailed and interpreted at the 5 perthe AERS began in November of that year, and cent level. If inspection of these data revealed data for 2008 involve only eight months because that reporting frequencies were higher than we requested adverse event reports up to and expected for any one drug, we then analyzed the including August 2008. Articaine was introduced data further with that drug excluded. into the U.S. market in May 2000. Therefore, as expected, no cases were reported for this drug RESULTS before this time. As shown in Figure 1, the During the period from November 1997 through majority of adverse events reported before the August 2008, 11,003 adverse events were year 2000 involved prilocaine. After 2000, the 35 NUMBER OF CASES C 838 JADA, Vol. 141 July 2010 Copyright © 2010 American Dental Association. All rights reserved. Reprinted by permission. C O V E R S T O R FREQUENCY OF PARESTHESIA number of reported cases involving articaine increased markedly, and articaine became the Prilocaine 6 Percent local anesthetic most reported to be associated Articaine with paresthesia across the entire study period. Mepivacaine 14 Percent 18 Percent We obtained the yearly U.S. sales of local anesthetics from 1997 through 2008; Figure 2 shows Bupivacaine the relative percentage of each anesthetic’s 4 Percent market share during this period. These sales data provided a basis for determining an expected distribution of paresthesia reports if the null hypothesis was correct and the type of local anesthetic Lidocaine administered had no effect on the development of 58 Percent this condition. Figure 3 shows the observed cases of paresthesia compared with the expected frequencies per drug. χ2 analysis showed that articaine and Figure 2. U.S. local anesthetic sales percentages from November prilocaine were the only two drugs associated 1997 through 2008. Source: Strategic Data Marketing, unpublished with a higher-than-expected frequency of paresdata, 2009. thesia (P < .0001 for each) on the basis of market share (Table 1). Cases involving prilocaine were 7.3 times 140 more numerous than expected and 120 those involving articaine 3.6 times more numerous than expected. Given 100 these findings, and in an attempt to more accurately identify whether each 80 of these two drugs had individual significance, we then analyzed data for 60 both articaine and prilocaine with the other drug excluded from calculations 40 to determine if significance remained. Table 2 shows the results of this further 20 analysis: the χ2 values for prilocaine 0 and for articaine increased, demonArticaine Bupivacaine Lidocaine Mepivacaine Prilocaine strating a highly significant difference DRUG when we compared the observed reports Expected Frequency Observed Frequency of paresthesia with the expected reports. Because articaine was introFigure 3. Expected versus observed frequency distribution per local anesthetic duced into the U.S. market in 2000, we drug from November 1997 through August 2008. repeated the analysis from that year on, as Table 3 (page 841) shows. Once again, χ2 the overall analysis from 1997 through 2008, analysis showed that each of these two drugs was shown in Tables 1 and 2, as we know that they reported to have caused neuropathy significantly occured within this study period, but we omitted more frequently than expected (P < .0001). them in the subanalysis from 2000 through 2008, Given this finding, as before, we analyzed shown in Tables 3 and 4, because of the uncerthese two drugs separately to test for any statistitainty of the year. Among cases reported from 1997 cally significant associations. This analysis through 2008, no year of occurrence was specified revealed that paresthesias associated with artifor four cases involving articaine, four cases caine and prilocaine were significantly greater involving lidocaine and 16 cases involving prilothan expected (P < .00000001) on the basis of caine. Although the cases involving articaine market share (Table 4, page 841). A number of almost certainly occurred from 2000 onward, we reports did not specify the year of the adverse used n = 112 instead of n = 116 in the subanalyses event occurrence. These cases were included in shown in Tables 3 and 4 to be consistent with the JADA, Vol. 141 Copyright © 2010 American Dental Association. All rights reserved. Reprinted by permission. July 2010 839 Y C O V E R S T O R Y to the AERS and the total number of cartridges sold in the United States Observed and expected* frequencies of during this 12-year period. The reported paresthesia as reported to the Adverse Event incidences were as follows: prilocaine, Reporting System involving dental local 1:2,070,678; articaine, 1:4,159,848; bupivacaine, 1:124,286,050; lidocaine, anesthetics from 1997 through 2008 in the 1:181,076,673; and mepivacaine, † United States. 1:623,112,900. The overall reported inciLOCAL ANESTHETIC OBSERVED EXPECTED dence was 1:13,800,970. FREQUENCY FREQUENCY Patients’ age and sex. The mean Articaine Comparison ‡ age of affected patients was 41.9 years, Articaine 116 31.86 and the age range was 15 to 78 years. Most of the cases reported involved Other anesthetics 110 194.14 patients in their third, fourth or fifth TOTAL 226 226 decades of life. In all, in cases in which § Prilocaine Comparison the sex of the patient was reported, 130 Prilocaine 97 13.26 involved female patients (61.0 percent), Other anesthetics 129 212.74 which was significantly greater than TOTAL 226 226 the 83 cases involving male patients * Observed frequency: Number of cases. Expected frequency: Total number of cases × frac(39.0 percent) (P < .01). tional use of specific drug. † Does not include cases involving the use of more than one agent (n = 22). Injection technique, arch and ‡ The difference was statistically significant (χ = 258.7, P < .0001). side. The particular injection technique § The difference was statistically significant (χ = 561.8, P < .0001). used was reported in 219 of the 248 TABLE 2 cases. Of these, 207 (94.5 percent) involved a mandibular nerve block, two Observed and expected* frequencies of (0.9 percent) involved a mental nerve paresthesia as reported to the Adverse Event block and 10 (4.6 percent) involved Reporting System involving articaine and infiltration. In 213 cases, the mandibular arch was affected (95.1 percent), in prilocaine from 1997 through 2008 in the 10 cases the maxillary arch was affected United States, analyzed with the other (4.5 percent) and in one case both arches significant drug excluded from the were affected (0.4 percent). Leaving out calculations.† the one case in which both arches were affected, significantly more cases LOCAL ANESTHETIC OBSERVED EXPECTED FREQUENCY FREQUENCY involved the mandibular arch than the ‡ maxillary arch (P < .0001). There was no Articaine Comparison predilection in terms of affected side Articaine 116 19.32 (when it was reported), with 46 cases Other anesthetics minus prilocaine 13 109.68 (52.3 percent) involving the right side TOTAL 129 129 and 42 cases (47.7 percent) involving Prilocaine Comparison § the left side (P = .67). Prilocaine 97 7.51 Affected area. Figure 4 (page 842) Other anesthetics minus articaine 13 102.49 shows the affected sites. Of 191 reports TOTAL 110 110 in which an affected anatomical struc* Observed frequency: Number of cases. Expected frequency: Total number of cases × fracture was identified, 170 cases involved tional use of specific drug. the tongue, which is innervated by the † Does not include cases involving the use of more than one agent (n = 22). ‡ The difference was statistically significant (χ = 569.0, P < .0001). lingual nerve. In 14 cases, the lower lip, § The difference was statistically significant (χ = 1,144.5, P < .0001). innervated by a branch of the inferior alveolar nerve, was affected. In seven analyses of the other drugs from 2000 onward. The cases, both were affected. result remains statistically significant either way. Injection events and other symptoms. PosiWe calculated the overall reported incidence of tive aspiration of blood or the feeling of electric paresthesia on the basis of the number of reports shock, which may indicate direct contact of the TABLE 1 2 1 2 1 2 1 2 1 840 JADA, Vol. 141 July 2010 Copyright © 2010 American Dental Association. All rights reserved. Reprinted by permission. C O V E R S T O R TABLE 3 needle with the nerve during injection, was reported in 18 cases (7.3 percent). Observed and expected* frequencies of Although all cases involved paresthesia, paresthesia as reported to the Adverse Event some of the reports indicated further Reporting System involving dental local symptoms—specifically, taste disturbance in 44 cases (17.7 percent) and anesthetics from 2000 through 2008 in the dysesthesia in 54 cases (21.8 percent). United States.† Type of dental procedure. We LOCAL ANESTHETIC OBSERVED EXPECTED assumed that if the treatment was not FREQUENCY FREQUENCY listed, surgery was not performed. Articaine Comparison ‡ Therefore, we performed the primary Articaine 112 25.01 analysis described above on the 226 single-drug cases to which this assump- Other anesthetics 22 108.99 tion applied. Of the 89 instances in TOTAL 134 134 which nonsurgical dental treatment Prilocaine Comparison § was identified, restorative dentistry Prilocaine 19 7.87 was most common, being performed in Other anesthetics 115 126.13 66 cases (74.2 percent). Scaling was TOTAL 134 134 reported in 10 cases (11.2 percent) and * Observed frequency: Number of cases. Expected frequency: Total number of cases × fracendodontic treatment was reported in tional use of specific drug. † Does not include cases involving the use of more than one agent (n = 10). 13 cases (14.6 percent). To control for ‡ The difference was statistically significant (χ = 372.0, P < .0001). the possibility that there were unidenti§ The difference was statistically significant (χ = 16.7, P < .0001). fied surgical cases within the unknown TABLE 4 procedures, we repeated analysis among the five drugs after eliminating Observed and expected* frequencies of all cases with unknown procedures in paresthesia as reported to the Adverse Event addition to the known surgical cases. Reporting System involving articaine and When we analyzed the data for the 89 known procedure cases only, we found prilocaine from 2000 through 2008 in the that both prilocaine and articaine still United States, analyzed with the other produced a greater-than-expected significant drug excluded from the reported incidence of neuropathy on the † basis of market share than did the other calculations. anesthetics (P < .0001), which was the LOCAL ANESTHETIC OBSERVED EXPECTED FREQUENCY FREQUENCY same finding as that in the primary Articaine Comparison ‡ analysis (n = 226). Finally, we performed an analysis including the 18 Articaine 112 22.81 surgical cases in which only one agent Other anesthetics minus prilocaine 3 92.19 was used (n = 244), with the results TOTAL 115 115 once again showing the same statistiPrilocaine Comparison § cally significant difference for prilocaine Prilocaine 19 1.59 and articaine (P < .0001). Other anesthetics minus articaine 3 20.41 Multiple drug injections. There TOTAL 22 22 were 22 cases of multiple drug injec* Observed frequency: Number of cases. Expected frequency: Total number of cases × fractions. The ordering of administration tional use of specific drug. was listed in only eight of these. In one † Does not include cases involving the use of more than one agent (n = 10). ‡ The difference was statistically significant (χ = 435.0, P < .0001). case, the clinician had used the lower§ The difference was statistically significant (χ = 205.5, P < .0001), but there was an concentration drug first, then the 4 perexpected value of less than 5. The difference was statistically significant (P < .00000001 according to exact binomial testing that was two-sided and used the method of small cent solution. In the other seven cases, P values). the clinician had used the 4 percent concentration first. contain a vasoconstrictor. Where this distinction Vasoconstrictor. Prilocaine and mepivacaine was reported, prilocaine plain constituted 28 of are marketed in formulations that are plain or the single-drug cases, and prilocaine with 2 1 2 1 2 1 2 1 JADA, Vol. 141 Copyright © 2010 American Dental Association. All rights reserved. Reprinted by permission. July 2010 841 Y C O V E R S T O R Y available for entering adverse event reports on Nov. 1, 1997. It replaced an 89.0 earlier system, the Spontaneous 90 Reporting System, that held reports 80 from 1968 through October 1998. 70 Because reports to AERS are voluntary, there is the likelihood of underre60 porting, and the true incidence most 50 likely is higher than that found in this 40 study. This phenomenon already has 30 been noted in the literature, with results from one meta-analysis showing 20 a median underreporting rate of 94 per7.3 10 3.7 cent, meaning that only 6 percent of 0 adverse events were reported.15 FurTongue Lower Lip Tongue and Lower Lip thermore, many dentists may not know AFFECTED STRUCTURES that the AERS exists and that they can report paresthesia to this national dataFigure 4. Distribution of structures affected by paresthesia. base. These factors likely could explain the large difference in incidence 1:200,000 epinephrine constituted 61 cases. Our reported by others.4-9 As a result, readers should database for sales of prilocaine did not distinconsider the paresthesia rates calculated here only guish between these two formulations, so we as an absolute minimum estimate of incidence. could not determine significance from these data. Nevertheless, the AERS is the only U.S. national There was only one single-drug report for mepivadatabase for this information, and its usefulness caine, which was the 3 percent plain solution. in corroborating the results of other studies has This low number does not allow significance to be been stated.16 determined. A potential concern is the possibility that Resolution. The duration of oral paresthesia reported rates of paresthesia may differ among was reported in 108 of the 248 cases. This period drugs because of a recognition bias, a reporting ranged from as little as one day to as many as 736 bias or both. This bias occurs when practitioners days. Confirmed resolution of paresthesia was preferentially report adverse reactions associated reported in only 34 of the 108 cases. Of the cases with certain drugs owing to recent attention in the of paresthesia that did resolve, 25 did so in less media or scientific literature.17,18 However, this than two months, with the remaining nine bias would not explain the high rates of reporting resolving within 240 days. for prilocaine in the late 1990s. This bias cannot be ruled out entirely for the reports involving artiDISCUSSION caine, but the magnitude of the increase, as shown Our results are consistent with those of reports in Figure 1, would tend to reduce the likelihood of from Canada and Denmark.4,5,8,9 Furthermore, this being the sole cause of the marked increase. they corroborate earlier findings that suggested Furthermore, we repeated the data analysis for all that the use of either prilocaine alone,6,13 articaine dental procedures conducted with and without alone8,9 or both drugs4,5,12 may be associated with surgery, as well as for all years and then for 2000 an increased risk of developing paresthesia. We onward only, and the results showed that both believe it is important to note that articaine and prilocaine and articaine were reported as being prilocaine are the only dental local anesthetics involved significantly more often than any other formulated as 4 percent solutions in the United local anesthetic for all of these analyses. Thus, no States, with all others being of lower concentramatter how we analyzed the data, the same assotion (bupivacaine is 0.5 percent, lidocaine is 2 perciation between prilocaine or articaine administracent and mepivacaine is either 2 or 3 percent). tion and increased risk of experiencing paresDatabases used. We used two databases for thesia remained. this study. The source for the reports of paresThe second database was the information thesia was the FDA’s AERS. This system became obtained by a marketing company, Strategic Data PERCENTAGE AFFECTED BY PARESTHESIA 100 842 JADA, Vol. 141 July 2010 Copyright © 2010 American Dental Association. All rights reserved. Reprinted by permission. C Marketing. The market share information provided by this company closely matches that already reported in the literature. Investigators in one study reported that the 2005 market shares were 47 percent for lidocaine, 26 percent for articaine, 15 percent for mepivacaine and 6 percent for prilocaine, with the reference cited as Septodont (Lancaster, Pa.), October 2006.10 In another study, the market shares cited for 2006 were 54 percent for lidocaine, 25 percent for articaine, 15 percent for mepivacaine and 6 percent for prilocaine, with the reference quoted as a September 2006 personal communication from Septodont.13 The data we obtained from Strategic Data Marketing listed the 2005 market shares as 53.2 percent for lidocaine, 23.4 percent for articaine, 13.5 percent for mepivacaine and 6 percent for prilocaine. For 2006, the shares the company listed were 55.4 percent for lidocaine, 25 percent for articaine, 12.9 percent for mepivacaine and 6 percent for prilocaine. Thus, our data were close to the estimates provided independently by investigators in two other studies,10,13 and therefore we can assume that these numbers are valid. Nerve involvement in paresthesia. Our results showed that the lingual nerve was involved in 89.0 percent of the reports, consistent with findings of previous studies.4,5,9,12 To determine why the lingual nerve is most commonly affected, investigators in a study published in 2003 examined the histologic characteristics of lingual nerves at the level of the lingula in 12 cadavers.19 That study’s results showed a range in the number of fascicles present, and the authors speculated that a unifascicular nerve may be injured more easily than one with multiple fascicles. Four of the 12 lingual nerves had one fascicle, whereas the inferior alveolar nerve was always multifascicular. To date, this appears to be the most plausible explanation for the finding of the predilection of the lingual nerve to develop paresthesia. The mechanism underlying nonsurgical paresthesia is not known. In a 2000 study, five patients with permanent paresthesia secondary to injection with local anesthetic underwent surgical exploration of their injuries; in all cases, there was no evidence of damage to the nerve caused by the anesthetic needle.6 Thus, mechanical trauma alone appears to be an unlikely cause. Could nerve damage be caused by neurotoxicity of the local anesthetic in combination with a minor trauma created by the needle? This is unknown, although results from previous studies suggest it O V E R S T O may be the cause.4,9 Supporting this theory is the finding that there is a great deal of in vitro and in vivo experimental evidence of a dose-dependent neurotoxicity associated with local anesthetics.20-29 To date, results from randomized controlled clinical trials generally have not shown that either 4 percent prilocaine or 4 percent articaine is superior to 2 percent lidocaine in achieving mandibular nerve block.30 Practitioners should take this equivalent benefit into account when comparing the relative risks of these drugs. CONCLUSION The findings of our study confirm that paresthesia arising from a local anesthetic injection alone is a rare event. Nevertheless, the findings we report herein support those published previously4-9 and show that the 4 percent anesthetic solutions used in dentistry, namely prilocaine and articaine, are more highly associated with the development of paresthesia than are those of lower concentration. Therefore, dentists should consider these results when assessing the risks and benefits of using 4 percent local anesthetics for mandibular block anesthesia. ■ Disclosure. None of the authors reported any disclosures. An abstract of this study is scheduled to be presented at the International Association for Dental Research General Session in Barcelona, Spain, in July 2010. These results constitute part of a thesis submitted by Dr. Garisto in conformity with the requirements for the degree of Master of Science in Dental Anesthesia at the University of Toronto. 1. Malamed SF. Handbook of Local Anesthesia. 5th ed. St. Louis: Mosby; 2004:288-289. 2. Haas DA. Localized complications from local anesthesia. J Calif Dent Assoc 1998;26(9):677-682. 3. Haas DA. Articaine and paresthesia: epidemiological studies. J Am Coll Dent 2006;73(3):5-10. 4. Haas DA, Lennon D. A 21 year retrospective study of reports of paresthesia following local anesthetic administration. J Can Dent Assoc 1995;61(4):319-320, 323-326, 329-330. 5. Miller PA, Haas DA. Incidence of local anesthetic-induced neuropathies in Ontario from 1994-1998 (abstract 3869). J Dent Res 2000; 79(special issue):627. 6. Pogrel MA, Thamby S. Permanent nerve involvement resulting from inferior alveolar nerve blocks (published correction appears in JADA 2000;131[10]:1418). JADA 2000;131(7):901-907. 7. Dower JS Jr. A review of paresthesia in association with administration of local anesthesia. Dent Today 2003;22(2):64-69. 8. Legarth J. Skader pa nervus lingualis opstaet i forbindelse med mandibularanalgesi: anmeldt til Dansk Tandlaegeforenings Patientskadeforsikring 2002-2004. Tandlaegebladet 2005;109(10): 786-788. 9. Hillerup S, Jensen R. Nerve injury caused by mandibular block analgesia. Int J Oral Maxillofac Surg 2006;35(5):437-443. 10. Malamed SF. Local anesthetics: dentistry’s most important drugs—clinical update 2006. J Calif Dent Assoc 2006;34(12):971-976. 11. Malamed SF. Articaine versus lidocaine: the author responds (comment on Dower JS Jr. Articaine vs. lidocaine. J Calif Dent Assoc 2007;35(4):240, 242, 244). J Calif Dent Assoc 2007;35(6):383-385. 12. Gaffen AS, Haas DA. Retrospective review of voluntary reports of nonsurgical paresthesia in dentistry. J Can Dent Assoc 2009;75(8):579. 13. Pogrel MA. Permanent nerve damage from inferior alveolar nerve blocks: an update to include articaine. J Calif Dent Assoc 2007;35(4): 271-273. JADA, Vol. 141 Copyright © 2010 American Dental Association. All rights reserved. Reprinted by permission. July 2010 843 R Y C O V E R S T O R Y 14. The National Security Archive. The Freedom of Information Act (FOIA). “”. Accessed Jan. 29, 2010. 15. Hazell L, Shakir SA. Under-reporting of adverse drug reactions: a systematic review. Drug Saf 2006;29(5):385-396. 16. Hochberg AM, Pearson RK, O’Hara DJ, Reisinger SJ. Drugversus-drug adverse event rate comparisons: a pilot study based on data from the US FDA Adverse Event Reporting System. Drug Saf 2009; 32(2):137-146. 17. Rawlins MD. Spontaneous reporting of adverse drug reactions: I—the data. Br J Clin Pharmacol 1988;26(1):1-5. 18. Stricker BH, Tijssen JG. Serum sickness-like reactions to cefaclor. J Clin Epidemiol 1992;45(10):1177-1184. 19. Pogrel MA, Schmidt BL, Sambajon V, Jordan RC. Lingual nerve damage due to inferior alveolar nerve blocks: a possible explanation. JADA 2003;134(2):195-199. 20. Fink BR, Kish SJ. Reversible inhibition of rapid axonal transport in vivo by lidocaine hydrochloride. Anesthesiology 1976;44(2):139-146. 21. Barsa J, Batra M, Fink BR, Sumi SM. A comparative in vivo study of local neurotoxicity of lidocaine, bupivacaine, 2-chloroprocaine, and a mixture of 2-chloroprocaine and bupivacaine. Anesth Analg 1982; 61(12):961-967. 22. Rigler ML, Drasner K. Distribution of catheter-injected local anesthetic in a model of the subarachnoid space. Anesthesiology 1991; 75(4):684-692. 844 JADA, Vol. 141 23. Lambert DH, Hurley RJ. Cauda equina syndrome and continuous spinal anesthesia. Anesth Analg 1991;72(6):817-819. 24. Kalichman MW, Moorhouse DF, Powell HC, Myers RR. Relative neural toxicity of local anesthetics. J Neuropathol Exp Neurol 1993; 52(3):234-240. 25. Selander D. Neurotoxicity of local anesthetics: animal data. Reg Anesth 1993;18(6 suppl):461-468. 26. Lambert LA, Lambert DH, Strichartz GR. Irreversible conduction block in isolated nerve by high concentrations of local anesthetics. Anesthesiology 1994;80(5):1082-1093. 27. Kanai Y, Katsuki H, Takasaki M. Graded, irreversible changes in crayfish giant axon as manifestations of lidocaine neurotoxicity in vitro. Anesth Analg 1998;86(3):569-573. 28. Cornelius CP, Roser M, Wietholter H, Wolburg H. Nerve injuries due to intrafascicular injection of local anesthetics experimental findings. J Craniomaxillofac Surg 2000;28(suppl 3):134-135. 29. Johnson ME, Saenz JA, DaSilva AD, Uhl CB, Gores, GJ. Effect of local anesthetic on neuronal cytoplasmic calcium and plasma membrane lysis (necrosis) in a cell culture model. Anesthesiology 2002; 97(6):1466-1476. 30. Yagiela JA. Local anesthetics. In: Yagiela JA, Dowd FJ, Johnson B, Mariotti A, Neidle EA, eds. Pharmacology and Therapeutics for Dentistry. 6th ed. St. Louis: Mosby; 2010:246-265. July 2010 Copyright © 2010 American Dental Association. All rights reserved. Reprinted by permission.

Disclaimer: Justia Dockets & Filings provides public litigation records from the federal appellate and district courts. These filings and docket sheets should not be considered findings of fact or liability, nor do they necessarily reflect the view of Justia.

Why Is My Information Online?