Effect of 4% topical lidocaine applied to the face on the serum levels of lidocaine and its metabolite, monoethylglycinexylidide

Background: Topical lidocaine is a common form of anesthesia for a wealth of procedures across a large number of disciplines, including laser treatments. Preparations can be purchased over the counter with no prescription necessary. It is considered a safer and more acceptable form of anesthetic than hypodermic injections; however, there have been reports of fatalities following its application. Above certain serum lidocaine concentrations, patients may experience effects of toxicity such as lightheadedness and paraesthesia; these effects can progress to seizures and cardiorespiratory depression, which can ultimately lead to death. The active metabolite of lidocaine, monoethylglycinexylidide (MEGX), can be almost as potent as lidocaine in terms of toxicity. Objectives: The authors examine the levels of both lidocaine and MEGX in blood serum after application of topical lidocaine. Methods: Twenty-five healthy volunteers were assigned to one of four groups (A, B, C, D). Group A had 2.5 g of 4% lidocaine topical anesthetic cream applied to the face for one hour without occlusion, Group B had 5 g applied to the face for one half-hour without occlusion, Group C had 5 g applied to the face for one hour without occlusion, and Group D had 5 g applied to the face for one hour with occlusion. To evaluate serum concentrations, blood was drawn every 30 minutes for four hours. Results: Group D showed the highest serum levels of lidocaine and MEGX, a three-fold increase compared with group C, which received the same dose (5g topical 4% lidocaine) but without occlusion. In group D, peak serum levels occurred at 90 minutes for serum lidocaine, which was also the fastest of the four groups. Serum MEGX levels peaked much later than serum lidocaine levels, at 210 minutes. Individual serum levels did not exceed 0.6 µg/mL. Across the groups, there was significant interindividual variation in both lidocaine and MEGX serum levels ( P = .061). Applications of 5 g of 4% lidocaine resulted in higher serum concentration of both lidocaine and MEGX. When comparing group A to group C, doubling the dose of 4% lidocaine from 2.5 g to 5 g resulted in double the serum levels of MEGX and a 50% increase in the serum lidocaine levels ( P = .021). When comparing groups C and D, the addition of an occlusive dressing resulted in a tripling of the serum lidocaine levels and a doubling of the serum MEGX levels, both of which were statistically significant ( P < .001). When comparing all four groups, there were significant differences between the combined serum concentrations of lidocaine and MEGX ( P < .001). Conclusions: Topical lidocaine preparations are increasingly being employed to provide a patient-friendly form of noninvasive analgesia for a multitude of procedures. Some preparations are available over the counter for unsupervised patient application. Our study has demonstrated significant interindividual variability for a given dose, especially when occlusion is applied. There have been fatalities resulting from topical lidocaine application, and our study suggests that this is the result of the unpredictability of lidocaine metabolism between individuals. Therefore, we recommend that caution be exercised with topical lidocaine preparations, in particular when applied in conjunction with occlusive dressings.