pH Levels of Unbuffered Solutions
The seven local anesthetic solutions tested, their lot numbers, and pH measurement ranges as reported by the manufacturer are shown in Table 1. In each case, two identical samples were prepared by injecting the contents of two cartridges (3.6 mL) into a clean and dry testing vial. All samples were tested four separate times using the same meter and process described above.
Buffering Local Anesthetic Solutions Using Sodium Bicarbonate
A 50-mL vial of sodium bicarbonate (8.4% sodium bicarbonate injection, USP, Hospira Inc. [www.hospira.com], lot number 41-143-EV) was used to buffer the seven local anesthetic solutions shown in Table 1. The buffered solutions were prepared using the same 9:1 ratio of local anesthesia to 8.4% sodium bicarbonate described by Malamed et al.6 A cartridge volume of 1.8 mL was used for all calculations when preparing the samples.8,9 In each case, 0.18 mL of local anesthetic solution was removed from the cartridge using a 0.5-mL insulin syringe with a 28-gauge 0.5-inch needle (Kendall Monoject Insulin Syringe, Tyco Healthcare, www.tyco.com, lot number 027501). Using a separate unused syringe, 0.18 mL of the commercially available sodium bicarbonate was removed from the 50-mL vial and immediately injected into the local anesthetic cartridge. The buffered local anesthetic solutions were immediately injected into a clean and dry testing vial for pH testing. Each sample consisted of 3.6 mL of buffered local anesthetic solution and was tested four separate times.
Buffering Local Anesthetic Solutions Using the Onpharma Mixing System
The samples were prepared using the Onpharma Mixing Pen, Onpharma Cartridge Connectors, and Onset Sodium Bicarbonate Injection, 8.4% USP Neutralizing Additive Solution. In all cases, the approved manufacturer mixing directions for the buffering of 2% lidocaine with epinephrine 1:100,000 were repeated for all the local anesthetic formulations tested (9:1 ratio of local anesthetic to 8.4% sodium bicarbonate).7 As per the study design, two separate 3.6-mL samples were created, and immediately after buffering were injected into a clean and dry mixing vial for pH testing. Each sample was tested four separate times.
pH Levels of Sodium Bicarbonate
Samples of the 50-mL vial of 8.4% sodium bicarbonate and the Onset Sodium Bicarbonate Injection, 8.4% USP Neutralizing Additive Solution were created by injecting 2 mL of each solution into a clean and dry testing vial. Two sets of samples were created for each solution; the pH level of each sample was tested four separate times.
Storage and Stability of Buffered Samples
Twenty-eight samples were created during the experiment, each in a separate testing vial (14 buffered samples using the 50-mL vial of sodium bicarbonate and 14 buffered samples using the Onpharma mixing system). All samples were stored by placing a cover over the vials. Each sample was retested after 3 days and again after 7 days. In all cases, the samples were hand mixed with a new mixing stick for 10 seconds before pH testing.
Reporting of Data
The pH values for each unbuffered sample are reported as means, and the buffered samples are reported as means with standard deviation. The pH values of the sodium bicarbonate solutions are reported as a mean with standard deviation.
The means of the buffered solutions were analyzed using a Student’s t-test. All calculations were done using Excel (Microsoft Office 2010, Microsoft Corp.).
The measured pH values for the seven tested local anesthetic solutions are shown in Table 2, column three. The pH levels of all of the local anesthetic solutions were within the labeled range as supplied by the manufacturer. The Xylocaine® solutions showed a higher pH reading (4.27 and 3.93) than those of the Articadent® solutions (3.62 and 3.68). The lowest pH value was for 4% Citanest with 1:200,000 epinephrine. For the solutions containing a vasoconstrictor (epinephrine), the pH level fell between 3.60 and 4.27. For the 3% Polocaine® and 4% Citanest® plain solutions, the pH value was 6.37 and 6.31, respectively.
In all cases after buffering, the pH values of the local anesthetic solutions increased. With hand-buffering, the average pH value increase was 2.4 ± 0.08 and the final buffered pH level on average was 6.9 ± 0.14. Buffering each local anesthetic using the Onpharma mixing system resulted in a similar average pH level increase of 2.5 ± 0.14 and the final buffered pH value on average was 7.0 ± 0.23. Individual buffered samples are reported as means with standard deviation in columns four and five of Table 2, depending on the mixing methodology. In all cases except one, 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® 1:50,000 epinephrine sample (P = .022), in which the Onpharma-mixed solution displayed a higher pH level than the hand-mixed solution.
Table 3 shows the pH level of local anesthetic solutions immediately after mixing, after 3 days, and after 7 days. In all cases, pH level of the buffered solutions continued to rise by day 3, and in most cases, rose just slightly more by day 7. Only 4% Citanest 1:200,000 epinephrine (following hand-mixing) showed a slight decrease in pH between the day 3 and day 7 recordings. The mean pH of the hand-buffered solutions at day 3 was 7.63 ± 0.29 with a mean increase from day 1 to day 3 of 0.71 ± 0.28. The mean pH value of the local anesthesia solutions using the Onpharma mixing system at day 3 was 7.56 ± 0.11 with a mean increase from day 1 to day 3 of 0.55 ± 0.09. In both cases the differences—between day-3 pH and pH increase from day 1 to day 3—were not statistically significant (P = .562 and P = .176, respectively).