I am pleased to be able to respond to Dr. Dower’s comments regarding our November JADA report of two clinical trials of 4 percent articaine 1:200,000 epinephrine. These two efficacy anesthesia trials, with an enrollment of 63 subjects each, were not statistically powered to assess safety data and did not include a 2 percent lidocaine 1:100,000 epinephrine comparator; furthermore, reported adverse events were only secondary outcome measures. I believe Dr. Dower’s reinterpretation has misconstrued our reported safety findings.
First, it should be noted that we purposely did not categorize any of the reported adverse drug reactions (ADRs) by using the term "paresthesia," a term that often is misinterpreted by clinical subjects and dental professionals. Dr. Dower,1 in his reinterpretation of Haas and Lennon’s2 data, has used a definition for paresthesia appropriate for local anesthesia: "persistent anesthesia (anesthesia well beyond the expected duration), or altered sensation (tingling or itching) well beyond the expected duration of anesthesia."
However, Stedman’s Online Medical Dictionary3 defines paresthesia in more general medical terms that do not stipulate duration: "an abnormal sensation, such as of burning, pricking, tickling, or tingling." Others have used categories of dysesthesia and hyperesthesia.4 To avoid confusion with definitions, and to capture as many potentially neurotoxic events as possible, we recorded any reported symptom of "numbness or tingling" both immediately after the termination of the study and 24 hours after administration.
Second, Dr. Dower implies that, as a sponsored investigator, I may have underreported my ADR data regarding "tingling and numbness." He notes that my article reported two events, whereas Table 2 of the package insert for articaine lists three. It is clear that the two trials we described involved only 126 subjects (63 receiving mandibular blocks and 63 receiving maxillary infiltrations), whereas Table 2 of the package insert describes the incidence of adverse events among 361 subjects (n = 182 and n = 179). Table 2, prepared and approved by the U.S. Food and Drug Administration (FDA), includes the cumulative adverse event data from two additional clinical trials.5,6
The total number of subjects in these four trials was 361. Each of these subjects received at least two injections, and some received as many as seven injections. The cumulative results of these four studies do indeed report a total of three "numbness and tingling" ADRs, as shown in Table 2 of the package insert.
Detailed descriptions of each of these three ADRs are provided in the text of the articles.5–7 Two are best characterized as trauma to oral soft tissue—one possibly the result of cheek retraction during periodontal surgery, and one located on the medial aspect of the mandibular ramus at the site of needle insertion for inferior alveolar nerve block. Neither followed a mandibular or maxillary sensory distribution, and both resolved within 24 hours. The third was described as prolonged local anesthesia of the lip that resolved within six hours. According to Dr. Dower’s definition, none of these would be correctly defined as persistent local anesthetic-induced "paresthesias."
I do not feel it is appropriate for me to respond to Dr. Dower’s criticism of Dr. Malamed’s articles. Nor do I have any knowledge of the rationale for the FDA’s decision to revise the package insert information. References selected in our article were limited to well-designed studies using original data.
I recognize that Dr. Dower maintains an active dialogue regarding the risk of nerve damage associated with local anesthesia, and I agree that carefully designed prospective, multi-center research projects are needed to elucidate the cause, risk factors and true incidence of this important, albeit rare, outcome.
Risk assessment for making clinical decisions requires accurate and valid information. Acquiring this kind of data for rare clinical events is extremely difficult.8 However, misinterpreting other investigators’ data can only hinder our understanding of the best practice of dentistry. A careful appraisal of our published ADR data5–7 provides no scientific support for Dr. Dower’s speculations.
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