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Increasing the pH of lidocaine reduces patients’ pain and discomfort on injection.

Sachin Seth DDS .


Systematic Review Conclusion

A robust meta-analysis of 23 double blinded, randomized controlled trials showed that increasing the pH of lidocaine reduces a patient's pain and discomfort.

Critical Summary Assessment

Increasing the pH of lidocaine solution with sodium bicarbonate may be considered in decreasing pain on injection and augment patients' comfort and satisfaction.

Evidence Quality Rating

Good Evidence

Structured Abstract

Clinical Questions:

In adults and children, does adjusting the pH of lidocaine affect pain resulting from non-intravascular injections?

Review Methods:

Four authors independently screened the titles and abstracts resulting from a search of six electronic databases with no language restrictions. Inclusion criteria comprised only double blind, randomized controlled trials.. They did not exclude studies because of participants’ ages, underlying disease, condition or diagnosis, and did include healthy people in need of local anaesthesia such as those undergoing dental procedures. Studies that used lidocaine mixed with other anesthetics, anesthetics other than lidocaine, temperature variances between interventions or the site rather than the patient as the unit of analysis were rejected. The primary outcome studied was pain intensity as measured using a visual analogue scale (VAS). A secondary outcome of patient preference was also analyzed. The authors judged the quality of the studies on the method of randomization and allocation concealment. Using a random effects model of heterogeneity, the authors separately analyzed studies with low and high risk of bias due to allocation concealment, as well as studies that used injection volumes lower than 2.5 mL.

Main Results:

Twenty-three double-blind, randomized controlled trials fulfilled the inclusion criteria. Ten studies (n= 685) were parallel-group design and 13 were crossover studies (n= 432). The authors analyzed these designs separately. All studies were described as being double blind; however, upon closer assessment the method of blinding was unclear in three studies. Pain associated with the injection of buffered lidocaine solution was less than pain associated with unbuffered solution. In crossover studies, the difference was -1.98 units (95 percent CI, -2.62 to -1.34) of the 10-point VAS, and in parallel-group studies, it was -0.95 units (95 percent CI, -1.49 to -0.47). The pooled odds ratio for patients' preference to buffered compared to non-buffered lidocaine was 3.01 (95 percent CI, 2.10 - 4.15).


Increasing the pH of lidocaine solution decreased pain on injection and augmented patient comfort and satisfaction.

Source of Funding:

Not stated.


Importance and Context:

Lidocaine is an amide-type local anesthetic commonly used in dental procedures due to its rapid onset, safety and low cost.(1) Because of these features, it represents the "gold standard" by which other anesthetics are compared.(2) However, lidocaine preparations can range in pH from 3.5 to 4.5,(2) which is thought to attribute to some of the discomfort the patient experiences on injection (human physiologic pH is approximately 7.4). The pain and burning associated with a lidocaine injection likely results from the increase in hydrogen ions in the tissues adjacent to the injection site due to the acidic nature of the injected solution (3-6).

Strengths and Weaknesses of the Systematic Review:

The authors conducted a high quality systematic review that included a comprehensive search of major electronic databases with no language restrictions. They established succinct inclusion/exclusion criteria that included only double-blind, randomized controlled trials. The potential contribution to bias in these studies could have been investigated through sensitivity analysis. To address heterogeneity, the authors separated the analyzed studies into low and high risk of bias due to level of allocation concealment, use of low and high volumes of injection and use of lidocaine for different types of procedures. The presence of epinephrine, needle size and speed of injection also contributed to heterogeneity. This systematic review did not evaluate the effect alkalization of lidocaine has on the quality of the sensory nerve block.

Strengths and Weaknesses of the Evidence:

All studies selected for this review were identified as being double blind, the method of blinding for three of the studies was unclear. The authors analyzed parallel and crossover trials separately. Sixteen of the 23 studies had a low risk of bias. Although they analyzed the factors that explain heterogeneity, with the exception of patient preference, the results remained heterogeneous (I2 = 90 percent for crossover trials and 87 percent for parallel-group).

Implications for Dental Practice:

The evidence suggests that increasing the pH of lidocaine solution with sodium bicarbonate decreases pain on injection and augments patient comfort and satisfaction. The authors could not offer an explanation as to why there was a large variation in the magnitude of pain abatement. Consequently, further investigation needs to be done as to the conditions in which buffered lidocaine has the greatest benefit. Additionally, oral trials must be performed to ascertain the benefits for dental anesthesia. As the presence of the buffering solution reduces the stability of anesthetics, researchers need to develop a delivery method by which the buffering and lidocaine solutions remain separate until injection. 1. Corbett IP, Ramacciato JC, Groppo FC, Meechan JG. A survey of local anaesthetic use among general dental practitioners in the UK attending postgraduate courses on pain control. Br Dent J 2005;199(12):784-7; discussion 78. 2. Malamed S. Handbook of Local Anesthesia, 5th Ed. St. Louis, MO: Elsevier; 2004. Pages 63-66. 3. Issberner U, Reeh PW, Steen KH. Pain due to tissue acidosis: a mechanism for inflammatory and ischemic myalgia?. Neuroscience Letters 1996;208(3):191–4. 4. Steen KH, Reeh PW, Anton F, Handwerker HO. Protons selectively induce lasting excitation and sensitization to mechanical stimulation of nociceptors in rat skin, in vitro. Journal of Neuroscience 1992;12:86–95. 5. Steen KH, Reeh PW. Sustained graded pain and hyperalgesia from harmless experimental tissue acidosis in human skin. Neuroscience Letters 1993;154:113–6. 6.Steen KH, Issberner U, Reeh PW. Pain due to experimental acidosis in human skin: evidence for nonadapting nociceptor excitation. Neuroscience Letters 1995;199(1): 29–32.

Critical Summary Publication Date:


These summaries are not intended to, and do not, express, imply, or summarize standards of care, but rather provide a concise reference for dentists to aid in understanding and applying evidence from the referenced systematic review in making clinically sound decisions as guided by their clinical judgment and by patient needs. American Dental Association © 2018