May 2016
Volume 37, Issue 5

The mean pH value of the hand-buffered solutions at day 7 was 8.06 ± 0.34 with a mean increase from day 3 to day 7 of 0.43 ± 0.30. The mean pH value of the local anesthesia solutions using the Onpharma mixing system was 7.82 ± 0.27 with a mean difference from day 3 to day 7 of 0.26 ± 0.23. In both cases the differences—between day-7 pH value and pH increase from day 3 to day 7—were not statistically significant (P = .169 and P = .257, respectively).

Table 4 shows the results of pH testing of sodium bicarbonate used to buffer local anesthetic solutions (50-mL vial of 8.4% sodium bicarbonate injection, USP, Hospira Inc., lot number 41-143-EV) and Onset Sodium Bicarbonate Injection, 8.4% USP Neutralizing Additive Solution (lot numbers W0007328 and W0007361). No statistically significant difference was noted between the pH values of both of these solutions.


The aim of this study was to compare the ability to buffer the pH values of seven commercially available local anesthetic preparations using a simple chairside hand-mixing technique with commercially available 8.4% sodium bicarbonate versus the commercially available Onpharma mixing device with the Onset Sodium Bicarbonate Injection, 8.4% USP Neutralizing Additive. To the authors’ knowledge this is the first study to compare buffering of local anesthetics by these techniques. The literature is scant in regards to buffering articaine despite the growing popularity of this local anesthetic in clinical practice, and this is an avenue for future research. A secondary endpoint focused on the stability of the different buffered mixtures over time.

Manufacturers typically define a target pH value range at which local anesthetic preparations meet good manufacturing practices to be sold, and in this study all of the tested local anesthetic solutions, supplied by DENTSPLY Pharmaceutical, were within the appropriate ranges (Table 1). Under normal conditions local anesthetics exist in two forms: a charged form that is soluble in water and an uncharged, base form that is insoluble in water. The relative proportion of these two forms is dependent on the pH value of the solution and can be calculated using the Henderson-Hasselbalch equation.2

For solutions containing a vasoconstrictor (Xylocaine®, Articadent®, and Citanest®), the pH range can be approximately 3 to 5. Because of the ratio of charged-to-uncharged form of the local anesthetic molecule at lower pH value, the non-active, non-lipid soluble form dominates. After injection and prior to onset of anesthetic action, the body’s physiologic pH level naturally alkalinizes the local anesthetic solution, allowing for a greater proportion of the uncharged lipid soluble form. (Even at physiologic pH levels, a roughly 70:30 charged-to-uncharged ratio exists.) Therefore, low pH values may contribute to local anesthetic latency because of the time it takes the body to alkalinize low pH solutions for better local anesthetic solubility, and it may also contribute to injection-site pain because of soft-tissue injury.3,10

However, because they do not contain a vasoconstrictor and the preservative metabisulfite, plain solutions (Citanest® and Polocaine®) are available from the manufacturer at a higher pH range (closer to physiologic pH levels), which may account for their faster onset of action and less injection-site pain.11 This may also explain why both buffering techniques resulted only in a minimal pH value change following mixing with either sodium bicarbonate solution. It is unlikely, then, that buffering of plain solutions is of additional value in clinical situations.

Because the uncharged base form of local anesthetics is lipid soluble and will readily cross nerve membranes, alkalinization of solutions to drive the stoichiometric equation toward more uncharged local anesthetic molecules should lead to a faster, more effective, and profound local anesthesia clinically.1,11 Two early in vitro studies showed that buffering local anesthetics with sodium bicarbonate can potentiate their nerve impulse-blocking action on peripheral nerves.4,5 These early studies led to the development of the Onpharma Mixing Pen, Onpharma Cartridge Connectors, and Onset Sodium Bicarbonate Injection, 8.4% USP Neutralizing Additive Solution as a convenient device for chairside mixing and delivery of buffered lidocaine.

A recent in vivo study by Malamed et al6 utilizing the Onpharma mixing system demonstrated a statistically significant decrease in onset time when patients received buffered lidocaine with epinephrine compared with an unbuffered solution. In this study, the time it took for 70% of participants to achieve pulpal anesthesia after administration of buffered and unbuffered lidocaine was 1:57 minutes and 8:30 minutes, respectively. These findings are consistent with Tortamano and colleagues12 who found mean onset of pulpal anesthesia for lidocaine with epinephrine to be 8:42 ± 3:06 minutes.

As shown in Table 2, in all samples after buffering, the pH levels of the local anesthetic solutions increased. With hand buffering, the average pH-value increase was 2.4 ± 0.08 and the final buffered pH value on average was 6.9 ± 0.14. Buffering each local anesthetic using the Onpharma mixing device resulted in a similar average pH-value increase of 2.5 ± 0.14 and the final buffered pH level on average was 7.0 ± 0.23. In both cases, the differences—between mean pH and the mean increase in pH—were not statistically significant (P = .345 and P = .129, respectively). Individual buffered samples are reported as means with standard deviation in Table 2, columns four and five, depending on the mixing methodology. In all but one of the cases, the difference in means of the buffered solutions when comparing the hand-mixed formulations to the Onpharma-mixed solutions were not significant as calculated using a Student’s t-test analysis (Table 2, column six). The one exception was the 2% Xylocaine with 1:50,000 epinephrine sample (P = .022) in which the Onpharma device was able to raise the pH level of the commercially available product from 3.93 to 7.09 ± 0.10 versus the hand-mixed formulation, which could only raise the pH value to 6.90 ± 0.10. Because this was a nonclinical study, it could not be concluded that this difference was clinically significant; however, it was a noteworthy finding.

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