Do some local anesthetics have a greater risk of producing nerve damage (e.g., paresthesia)?
Discussion in dental circles continues regarding 4% local anesthetic formulations and the reported incidence of paresthesia. Such concern started in 1995 with the publication of a paper by Haas and Lennon,7 which stated the incidence of paresthesia following all local anesthetic solutions with 1 : 785,000. For 0.5%, 2%, and 3% local anesthetic, the calculated risk was 1 : 1,125,000, and for 4% local anesthetics, it was 1 : 485,000. A subsequent retrospective study from Denmark provided similar results.8 Neither publication presents scientific documentation that 4% solutions are the cause of the paresthesia. Hillerup reported that 79% of the cases of paresthesia involved the lingual nerve, and 21% the inferior alveolar.8 Malamed, responding to Hillerup’s paper, suggested that the likely cause of lingual nerve damage associated with inferior alveolar nerve block administration is direct needle trauma to the lingual nerve, which lies directly in the path of needle insertion.9 In response to the Hillerup paper, the Pharmacovigilance Committee of the European Union initiated an inquiry into these allegations. Its report, released on October 20, 2006, concluded, “Regarding articaine, the conclusion is that the safety profile of the drug has not significantly evolved since its initial launch (1998). Thus, no medical evidence exists to prohibit the use of articaine according to the current guidelines listed in the summary of product characteristics.”10 The Committee further reported, “All local anaesthetics may cause nerve damage (they are neurotoxic in nature). Nerve injuries may result from several incidents: mechanical trauma due to needle insertion, direct toxicity from the drug, and neural ischaemia.” Their concluding statement read as follows: “There is no need for new experimental studies or clinical trials.”
Another possible “etiology” of these reports, especially as related to articaine HCl, is a phenomenon in epidemiology known as the Weber effect, after Dr. J.C.P. Weber.11 The Weber effect states that the number of reported adverse reactions to a drug rises until about the middle to the end of the second year of marketing; it peaks and then steadily declines, despite steadily increasing prescribing rates. The validity of the Weber effect has been demonstrated in many studies of adverse drug reactions.12,13
In 2007, Pogrel reported on 57 nonsurgical dental patients whom he evaluated for post–dental care paresthesia over a 3-year period.14 He commented in the introduction to the paper, “We were aware of the discussion in dental circles as to the use of articaine for inferior alveolar nerve blocks, and are aware of recommendations suggesting that it not be used for IANBs. This was the predominant reason for submitting this paper at this time.” Lidocaine was responsible for 35% of the cases of paresthesia, articaine and prilocaine each 29.8%. However, at the time the paper was published (2007), lidocaine had approximately a 54% share of the U.S. local anesthetic market, giving it a risk of paresthesia below that which would be calculated if all drugs were equally neurotoxic. The lidocaine ratio was 0.64. Prilocaine, with a 6% market share, had a ratio of 4.96—the highest of any of the local anesthetics in use in the United States, and articaine, at the time possessing a 25% market share, had a ratio of 1.19.14 Pogrel concluded, “Therefore, using our previous assumption that approximately half of all local anesthetic used is for inferior alveolar nerve blocks, then on the figures we have generated from our clinic we do not see disproportionate nerve involvement from articaine.”14
In 2010, Garisto and associates published a report on the occurrence of paresthesia in the United States.15 Although again demonstrating that 4% solutions had a higher reported rate of paresthesia, their reported incidences for all local anesthetics were quite astounding: the overall incidence of reported paresthesia was 1 in 13,800,970 injections. For mepivacaine, the incidence was 1 : 623,112,900, and for lidocaine, 1 : 181,076,673. For articaine and prilocaine, investigators reported 1 : 4,159,848 and 1 : 2,070,678, respectively. This author might report, for the sake of comparison, that the risk of being struck by lightning in the United States on an annual basis is 1 : 750,000.16
A meta-analysis comparing articaine HCl with lidocaine (lignocaine) HCl reported that articaine is more likely than lidocaine to achieve anesthetic success in the posterior first molar area, and that there is no difference in postinjection adverse events.17 A 2011 review of the articaine literature (116 papers reviewed) concluded, “although there may be controversy regarding its safety and advantages in comparison to other local anaesthetics, there is no conclusive evidence demonstrating neurotoxicity or significantly superior anaesthetic properties of articaine for dental procedures.”18