Forty adult subjects participated in this study. The subjects were in good health and were not taking any medications that would alter pain perception. Exclusion criteria were as follows: younger than 18 years of age; allergies to mannitol, local anesthetics, or sulfites; pregnancy; history of significant medical conditions (ASA Class II or higher); taking any medications (over-the-counter pain-relieving medications, narcotics, sedatives, antianxiety, or antidepressant medications), which may affect pain assessment; active pathosis at the site of injection; and inability to give informed consent. The Ohio State University Human Subjects Review Committee approved the study and written informed consent was obtained from each subject.
Using a crossover design, 40 adult subjects received 3 IAN blocks in 3 separate appointments spaced at least 1 week apart. These blocks consisted of: a 1.8 mL solution of 36 mg lidocaine with 18 µg epinephrine (control solution); a 2.84 mL solution of 36 mg lidocaine with 18 µg epinephrine (1.80 mL) plus 0.5 M mannitol (1.04 mL); and a 5 mL solution of 63.6 mg lidocaine with 32 µg epinephrine (3.18 mL) plus 0.5 M mannitol (1.82 mL).
Equal numbers of mandibular right and left sides were tested, with the first and second molars, first and second premolars, and lateral and central incisors chosen as the test teeth.
With the crossover design, 120 IAN blocks were administered and each subject served as his or her own control. The same side chosen for the first IAN block was used again for the second and third IAN blocks. The mandibular contralateral canine was used as the control to ensure that the pulp tester was operating properly and that the subject was responding appropriately. A visual and clinical examination was conducted to ensure that all teeth were free of caries, large restorations, crowns, periodontal disease, and that none had a history of trauma or sensitivity.
Before the injection at each of the 3 appointments, the experimental tooth and the contralateral canine (control) were tested 3 times with the electric pulp tester (Kerr, Analytic Technology Corp, Redmond, Wash) to ensure tooth vitality and obtain baseline information. The teeth were isolated with cotton rolls and dried with an air syringe. Toothpaste was applied to the probe tip, which was placed in the middle third of the buccal or labial surface of the tooth being tested. The value at the initial sensation was recorded. The current rate was set at 25 seconds to increase from no output (0) to the maximum output (80). Trained personnel, who were blinded to the anesthetic formulations, administered all preinjection and postinjection tests.
Before the experiment, the 3 anesthetic formulations were randomly assigned 5-digit numbers from a random number table. Each subject was randomly assigned to each of the 3 anesthetic formulations to determine which formulation was to be administered at each appointment. Only the random numbers were recorded on the data collection sheets to further blind the experiment.
The anesthetic formulations were prepared immediately prior to injection as follows. Under sterile conditions, 1.8 mL of 2% lidocaine with 1
100,000 epinephrine was drawn from standard dental cartridges (Astra Pharmaceuticals Products Inc, Westborough, Mass) into a 5 mL Luer-Lok disposable syringe (Becton-Dickinson & Co, Rutherford, NJ). All solutions used were checked to ensure that they had not expired. The 1.8 mL formulation contained 36 mg of lidocaine with 18 µg epinephrine. For the second formulation, 1.8 mL of 2% lidocaine with 1
100,000 epinephrine was drawn into a 5 mL syringe as described above. Using a 1 mL tuberculin syringe (Becton-Dickinson), 1.04 mL of 0.5 M mannitol was withdrawn from a 50 mL vial of a 25% (12.5 g/50 mL) supersaturated mannitol solution (American Regent Laboratories Inc, Shirley, NY) and was added to the 5 mL syringe. The syringe was then inverted 20 times to mix the solution. Each vial of mannitol solution was used only once. Before the mannitol was added to the syringe containing the lidocaine with epinephrine, the 50 mL vial was heated in a water bath (Teledyne Hanau, Buffalo, NY) to 80°C for 15 minutes to dissolve any crystals present in the supersaturated solution. The vial was then allowed to cool to room temperature before use. The 2.84 mL formulation contained 36 mg of lidocaine with 18 µg of epinephrine (1.8 mL) plus 0.5 M mannitol (1.04 mL). For the third formulation, 3.18 mL of 2% lidocaine with 1
100,000 epinephrine was drawn into a 5 mL syringe as described above. Added to this same syringe was 1.82 mL of the 0.5 M mannitol. The syringe was then inverted 20 times to mix the solution. The 5 mL formulation contained 63.6 mg of lidocaine with 32 µg epinephrine (3.18 mL) plus 0.5 M mannitol (1.82 mL). No precipitate formed when the mannitol was combined with the lidocaine. Selected components and selected final anesthetic formulations had their pH values determined using a pH/millivolt meter (Orion Research Inc, Boston, Mass).
The following calculations were utilized to determine the molarity for the final volumes of the lidocaine/mannitol formulations. Molarity (M), or molar concentration, is defined as a ratio between the number of moles of a solute per liter of solution. The mole of a compound is the amount of the compound in grams equal to its molecular weight. Therefore, the number of moles in 12.5 g of mannitol would be: moles of mannitol
12.5 g (per 50 mL vial) × 1 mol/182.17 g (molecular weight of mannitol)
0.0686 moles. The molarity of the mannitol solution used in this study was: molarity
0.0686 moles mannitol/0.05 L solution
1.372 M. Because the solutions were diluted by the lidocaine with epinephrine solution, the final molarity was calculated from the molarity after dilution using the following formula: (Mi) (Vi)
(Mf)(Vf) where Mi was the initial molarity multiplied by Vi (the initial volume), which was equal to Mf (the final molarity) multiplied by Vf (the final volume). Therefore, for the second formulation the calculated molarity of 0.5 M mannitol required the following volumes: (1.372 M)(X)
(0.5 M)(2.84 mL)
1.04 mL of mannitol. For the total volume of 2.84 mL of a 0.5 M mannitol formulation, 1.8 mL of lidocaine was combined with 1.04 mL of mannitol. For the third formulation, the calculated molarity of 0.5 M mannitol required the following volumes: (1.372 M)(X)
(0.5 M)(5.00 mL)
1.82 mL of mannitol. For the total volume of 5 mL of a 0.5 M mannitol formulation, 3.18 mL of lidocaine was combined with 1.82 mL of mannitol.
A standard IAN block23
was administered with a 27-gauge 1½-inch needle (Monoject; Sherwood Medical, St Louis, Mo) using each anesthetic formulation. Following needle penetration, and as the needle was advanced during placement, 0.2 mL of solution was deposited. After the target area was reached and aspiration was performed, 1 minute was used to deposit all anesthetic formulations, and the subject was asked to rate the pain of solution deposition. The pain scale was from 0 to 3. Zero indicated no pain. One indicated mild pain, pain that was recognizable but not discomforting. Two indicated moderate pain, pain that was discomforting but bearable. Three indicated severe pain, pain that caused considerable discomfort and was difficult to bear. The principal investigator (R.W.) performed all IAN injections.
At 1 minute after the IAN block, the first and second molars were pulp tested. At 2 minutes, the first and second premolars were tested. At 3 minutes, the central and lateral incisors were tested. At 4 minutes, the control canine was tested. This cycle of testing was repeated every 4 minutes for 60 minutes. At every fourth cycle the control tooth (the contralateral canine) was tested with a pulp tester without batteries to test the reliability of the subject. If the subject responded positively to an inactivated pulp tester, then they were not reliable and could not be used in the study. Subjects were asked if their lips and tongues were numb every minute for 5 minutes and at every fourth minute during pulp testing. If profound lip numbness was not recorded within 5 minutes, the block was considered unsuccessful and the subject was then reappointed. Two of 120 (1.7%) IAN blocks were unsuccessful in this study and these subjects required an additional appointment. All testing was stopped at 60 minutes postinjection.
All subjects completed postinjection surveys after each IAN block administered. The subjects rated pain in the injection area, using the previous pain scale (none, mild, moderate, severe), immediately after the numbness wore off, and again each morning upon arising for 3 days. The subjects were also asked to record subjectively any additional comments or side effects not relating to pain.
No response from the subject at the maximum output (80 reading) of the pulp tester was used as the criterion for pulpal anesthesia. Mean percent total pulpal anesthesia was defined as the total of all the times of pulpal anesthesia (80 readings) over the 60 minutes. With a nondirectional alpha risk of 0.05 and assuming a standard deviation of 32 and a correlation of 0.60, a sample size of 40 subjects was required to demonstrate a difference in anesthetic success of ± 15 percentage points with a power of 0.85.
Comparisons between the 3 formulations regarding mean percent total pulpal anesthesia were assessed using multiple Wilcoxon, matched-pairs, and signed rank tests adjusted using the step-down Bonferroni method of Holm. Comparisons between the 3 formulations regarding solution deposition pain and postinjection pain were made using the Friedman statistic. Comparisons were considered significant at P < .05.