Decreasing the pain of local anesthesia: a prospective, double-blind comparison of buffered, premixed 1% lidocaine with epinephrine versus 1% lidocaine freshly mixed with epinephrine

J Am Acad Dermatol. 2006 Jan;54(1):128-31. doi: 10.1016/j.jaad.2005.06.043.


Background: Local anesthetics are acidic and cause pain on infiltration into the skin. Two methods are commonly used by dermatologists to raise the pH of lidocaine with epinephrine: buffering with sodium bicarbonate or freshly mixing lidocaine with epinephrine on the day of use.

Objective: Our purpose was to compare the pain induced by infiltration of the skin with 1% lidocaine with epinephrine 1:100,000 buffered with sodium bicarbonate (buffered) versus 1% lidocaine freshly mixed with epinephrine (fresh).

Methods: Sixty volunteers were recruited for this prospective, double-blind study. Each subject received an intradermal injection of the buffered solution and the fresh solution. Immediately after each injection subjects rated the pain of infiltration on a 100-mm visual analog scale. The pain scores for the anesthetic solutions were compared using the paired t test.

Results: The pain score for the buffered solution was 18.3 +/- 20.3, and the pain score for the fresh solution was 23.5 +/- 19.1 (P = .0543). Sixty-five percent of subjects felt the fresh solution was more painful than the buffered solution.

Limitations: The results did not reach statistical significance.

Conclusion: In this small study, buffered lidocaine with epinephrine caused less pain on infiltration into the skin than lidocaine freshly mixed with epinephrine, but the results were not statistically significant.

Publication types

  • Controlled Clinical Trial

MeSH terms

  • Anesthetics, Local / administration & dosage
  • Anesthetics, Local / adverse effects*
  • Buffers
  • Double-Blind Method
  • Drug Combinations
  • Epinephrine / administration & dosage
  • Epinephrine / adverse effects*
  • Humans
  • Hydrogen-Ion Concentration
  • Injections, Intradermal
  • Lidocaine / administration & dosage
  • Lidocaine / adverse effects*
  • Pain / chemically induced*
  • Pain / physiopathology
  • Pain Measurement
  • Sodium Bicarbonate*
  • Solutions / chemistry


  • Anesthetics, Local
  • Buffers
  • Drug Combinations
  • Solutions
  • Sodium Bicarbonate
  • Lidocaine
  • Epinephrine