Topical anesthetics

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Review by Evan Schwarz, MD
Division of Emergency Medicine
Washington University in St. Louis

Eldelman A, Weiss JM, et al.  Topical anesthetics for dermal instrumentation:  a systematic review of randomized, controlled trials.  Annals of Emergency Medicine.  October 2005; 46 (4):  343-351.

    Earlier in the night, you saw a 41 year old with fever, headache, and neck pain.  The labs are back and it does not appear that he has meningitis.  You have just explained this to him, and are walking out of the room, when he complains to you that the LP hurt more than he had expected.  Last year he had an LP for the worst headache of his life and he barely felt a thing.  While initially shocked since you consider yourself one of the “nicer” docs in your group as you use eutectic mixture of local anesthetics (EMLA) prior to performing an LP, you begin to wonder if there is a superior product on the market.
    This meta-analysis included 25 randomized control trials.  The trials compared the efficacy of topical anesthetics to dermal infiltration with local anesthetics and also compared those topical anesthetics to EMLA.  The trials included both men and women who were 3 years old and above.  The authors felt 3 years was the lowest age that children could credibly quantify pain.  All trials had to use some validated pain score such as the visual analogue scale (VAS).  In order to minimize the variability in the meta-analysis, the trials could only involve certain superficial procedures (intravenous cannulation, venipuncture) or deeper instrumentation (arterial cannulation, lumbar puncture).  Studies involving non-intact skin (laceration repair) were not included.  Also all studies involving EMLA had to apply it for at least 45 minutes before the procedure.  The manufacturer suggests one hour, but per the authors, EMLA has been found to work after 45 minutes of application.
Ten trials compared EMLA to infiltration with local anesthetic with mixed results.  Five studies involved superficial procedures and five involved deep procedures.  In both subgroups the results were mixed with some trials showing a greater efficacy in EMLA and some showing dermal infiltration to be superior.  Because of significant heterogeneity, the studies involving deep infiltration were not statistically combined.  No study compared EMLA plus local infiltration to either one alone.  The EMLA patch was also compared to EMLA cream in 4 trials.  The analgesic efficacy of each product was found to be the same.  Two of these studies had their results statistically combined but still did not find a statistical difference on the visual analogue pain scale.
One study compared lidocaine ointment (xylocaine) to EMLA when used for analgesia in intravenous cannulation.  EMLA was found to be superior; however, it only included 7 patients.  Liposomal lidocaine cream (LMX) was also compared to EMLA in 2 studies.  Both studies found them to have an equivalent amount of analgesia.  In both studies EMLA was applied 60 minutes before the procedure and LMX was applied 30 minutes before the procedure.  Since LMX only had to be applied half as long to work just as well as EMLA, it was concluded to be preferable to EMLA.  When LMX was applied for 60 minutes, the patient did not receive a greater amount of analgesia compared to when it was applied for 30 minutes.  The studies used different pain scales so their results could not be combined.
One study compared tetracaine gel to local infiltration in arterial puncture and found comparable efficacy.  Four trials compared tetracaine gel versus EMLA.  In all 4 trials, topical tetracaine was found to provide greater analgesia than EMLA.  However in one of the trials, the difference was not statistically significant. Three trials used the VAS and had their results combined.  Once again a difference favoring tetracaine gel was found to be statistically significant.  However the weighted mean difference of 8.1 mm on the pain scale is less than the 13 mm other studies have found as the minimum decrease in pain that is clinically significant.
The last 2 studies compared liposomal encapsulated tetracaine (LET) to EMLA in superficial instrumentation.  Both trials concluded that LET had a greater efficacy even though one trial did not show a statistically significant difference.  When the results of the trials were combined, LET was concluded to be more efficacious.  While the results were statistically significant the difference was still less than the 13 mm found to be clinically significant.
While most results were mixed, the authors were able to draw some conclusions.  When EMLA was compared to local infiltration, there was no difference in analgesia.  However since the application of EMLA is painless, whereas local infiltration is painful, EMLA is preferable to local infiltration.  While LMX was not found to have an increase in analgesia compared to EMLA, it did offer two benefits.  First it only had to be applied half as long to work just as well.  Second LMX ($42 for 30 gram tube) is cheaper than EMLA cream ($51 for 30 gram tube). 


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