Introduction
There have been some documented serious adverse events and even fatalities after application of topical lidocaine.  This has been true for more than one of its preparations and all these cases when use was not supervised by medical personnel.  It is therefore imperative that the systemic absorption profiles of these drugs have been properly investigated.  This study looks at five commonly used preparations containing lidocaine.  Three of which are available over the counter without prescription; Topicaine, LMX 4 and a generic form of EMLA™ (2.5% lidocaine, 2.5 % prilocaine, produced by High tech Pharmaceutical, Amityville, NY).  The other two study drugs; BLT triple anesthetic cream and LET were compounded in pharmacy prior to use.   We compare the absorption of a fixed amount of each of the drugs when applied to the face, by measuring the serum levels of lidocaine and its metabolite monoethylglycinexylidide (MEGX).  In this way we hope to provide more information on the safety profile of the use of these drugs on facial skin.

Method:
25 subjects were enrolled in this IRB approved study.  Each subject in each group received 30g of the drug applied to the face and neck area.  This was then covered immediately with an occlusive dressing and left for 60 min.  The study drug was then removed.  Blood draws were taken via an intravenous catheter that was left in place for the duration of the study.  Bloods were drawn at 90, 120, 150, 240 and 480 minutes.  Any adverse events relating to the procedure were recorded. 

Results:
Drug absorption (figure 1):
The over the counter preparations had the highest serum lidocaine and MEGX levels.  On average Topicaine had the highest serum lidocaine and MEGX levels, 0.438µg/ml and 0.0678µg/ml respectively.   There were significant differences across the time points between the serum levels of lidocaine (p=0.0002) and MEGX (p=0.0045) when comparing all five groups.  For all study drugs there were still detectable levels of lidocaine and MEGX in the serum of participants at 8 hours. 

Inter-individual variation within the groups:
Inter-individual variation was shown between the individuals in each group except for LET.  Topicaine (p< 0.0001), EMLA (p< 0.0001), LMX-4 (p< 0.0001), and BLT (p=< 0.0001) all showed significant differences between the serum levels of MEGX and lidocaine combined in their respective groups.

Differences between 4% lidocaine containing preparations (figure 2):
Topicaine had the greatest serum absorption (0.491µg/ml) followed by LMX-4 (0.336 µg/ml) and then LET (0.038 µg/ml).  The differences between these three groups was statistically significant (p=0.0439).

Differences between preparations containing differing lidocaine concentrations (figure 3):
The 2.5% lidocaine containing preparation had greater absorption with a peak combined serum level of 0.4384µg/ml compared with 0.276µg/ml for the 4% containing preparations and 0.2232µg/ml for the 6% lidocaine containing preparation which had the least absorption.  The differences between the different lidocaine concentrations was statistically significant (p=0.0010)

Adverse skin reactions:
Two participants developed minor adverse reactions of erythema within the first 4 hours, with scaling and prolonged erythema at 48 hours, 1 in the Topicaine (4% lidocaine) group and 1 in the 2.5% lidocaine group (EMLA).  All skin reactions resolved by 7 days.  One subject in the Topicaine group developed a more severe skin reaction in the form of post inflammatory hyperpigmentation over the cheeks and dorsum of the nose.

Conclusions:
This study has shown that the over the counter (OTC) products which did not require prescription actually had greater levels of lidocaine in the bloodstream than the prescription drugs.  All adverse skin effects were seen with the OTC drugs.  This study has highlighted the effect of the drug delivery vehicle on the absorption through the skin.  We have also demonstrated that absorption of the drug through the facial skin varies from individual to individual.  The significance of this is that one cannot predict the amount of drug a patient will absorb.  Therefore, we would recommend that topical anesthetics are used under the supervision of a health care professional to avoid adverse toxic effects and in rare cases death.
A manuscript has been prepared based on the results detailed above and will be submitted for publication to Aesthetic Surgery Journal.