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Am Fam Physician. 2021;103(2):online

Clinical Question

Does a lower ratio of buffered lidocaine 1%/epinephrine 1:100,000 solution (Lido/Epi) to sodium bicarbonate (NaHCO3) solution cause less pain during infiltration?

Bottom Line

Lido/Epi buffered with NaHCO3 in a 3:1 ratio is significantly less painful during infiltration than unbuffered Lido/Epi and buffered Lido/Epi in a 9:1 ratio. The difference in mixing ratio does not change the length or quality of the anesthetic effect. There are no commercial products of Lido/Epi solutions with NaHCO3 because the stability of the mixture is limited. All injection solutions in this study were given at room temperature. (Level of Evidence = 1b)


Lido/Epi is one of the most commonly used local anesthetics for office-based procedures. The acidic nature of lidocaine is thought to be responsible for the burning sensation during infiltration. NaHCO3 is used as a buffering agent to minimize acidity and reduce pain during infiltration. The investigators recruited 48 healthy volunteers, 18 to 75 years of age, who randomly received (allocation concealed) either two or four infiltrations of 2-mL Lido/Epi buffered with NaHCO3 at room temperature in mixing ratios of 3:1, 9:1, or 10:0 (unbuffered), or a placebo (sodium chloride 0.9%). Mixing occurred within one minute before infiltration, and the injections randomly occurred on various sites of the right and left forearm. All participants completed the trial and no serious adverse events occurred. Study participants rated the 3:1 mixture as significantly less painful than the 9:1 mixture (median pain score is 1.5 points lower on a 10-point scale, where 0 = no pain and 10 = unacceptable pain, when 3:1 mixture is given first, and 0.5 points lower when given second). The unbuffered mixture was more painful than the 3:1 and 9:1 mixtures, and the placebo mixture was notably the most painful of all the injections.

Study design: Crossover trial (randomized)

Funding source: Foundation

Allocation: Concealed

Setting: Outpatient (specialty)

Reference: Vent A, Surber C, Graf Johansen NT, et al. Buffered lidocaine 1%/epinephrine 1:100,000 with sodium bicarbonate (sodium hydrogen carbonate) in a 3:1 ratio is less painful than a 9:1 ratio: a double-blind, randomized, placebo-controlled crossover trial. J Am Acad Dermatol. 2020;83(1):159–165.

POEMs (patient-oriented evidence that matters) are provided by Essential Evidence Plus, a point-of-care clinical decision support system published by Wiley-Blackwell. For more information, see Copyright Wiley-Blackwell. Used with permission.

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