Clinical parameters of the local anesthetic effects of bupivacaine applied with and without a vasoconstrictor in oral implantology

Background/Aim. Bupivacaine (Marcaine®), homologue of mepivacaine, chemically related to lidocaine, is used as a local anesthetic for local infiltration, peripheral nerve block, retrobulbar block, symphathetic block, and caudal and epidural anesthesia. The aim of this investigation was to determine and to compare clinical parameters of the local anesthetic effects of bupivacaine applied with and without a vasoconstrictor. Methods. This investigation included a total of 30 randomly selected patients, who ranged in age from 30−60 years, with partial or total anodontia in the molar region of the mandible. These patients with total or partial edentulous molar part of the mandible, scheduled for dental implantation placement, were asked to participate in the study. In the first phase of the investigation, the patients were subjected to local anesthesia with 3.5 cm3 of 0.5% bupivacaine with a vasoconstrictor (adrenalin, 1: 200 000) in the right side of the mandible. After administering local anesthesia, the placement of blade, cylindrical, transdental (B.C.T.) implants was performed. In the second stage of the investigation, in 7−10 days period after the first oral surgery, the patients were subjected to local anesthesia with 3.5 cm3 of 0.5% bupivacaine, but without a vasoconstrictor, in the left side of the mandible. After administering local anesthesia, the placement of B.C.T. implants was performed. During the performance of both oral surgery procedures, the following clinical parameters of the local anesthetic effects were monitored: latent period, duration and the potency of anesthesia, and the evaluation of the postoperative pain level. Results. The latent period under local anesthesia with 3.5 cm3 of 0.5% bupivacaine and vasoconstrictor was statistically significantly shorter than without vasoconstrictor. The duration of local anesthesia was longer without vasoconstrictor. There was no difference in the potency of anesthesia with or without a vasoconstrictor, while the lowest level of postoperative pain was found after administering bupivacaine without a vasoconstrictor use. Conclusion. The results of this investigation show that bupivacaine without a vasoconstrictor is efficient when used for local anesthesia in placing dental implants since it provides better blood circulation required for good dental implant osseointegration.


Introduction
Local anesthetics are the agents used to induce reversible blocking of the perception and transmission of pain in the limited areas of the body without the loss of consciousness 1−8 .They are capable of blocking transmission of impulse in any excitable cell and, in so doing, influence functioning of tissue, including sensory and motor peripheral nerves, autonomous ganglia, central nervous system (CNS), neuromuscular synapses, cardiac muscle and smooth muscles 9−11 .Local anesthetic solutions are the most widely used drugs in medicine and dentistry 12 .They prevent nociception generated during surgical and dental procedures 13 , and without them many medical and dental procedures could not be performed 14 .Local anesthetics are also used in diagnostics of some painful syndromes, as well as in idiopathic trigeminal neuropathy treatment 15,16 .A local anesthetic solution is basically composed of a local anesthetics and vasoconstrictor (most commonly adrenaline or noradrenaline) which raises the anesthetic effect of a solution 17−20 .Bupivacaine, a long-acting agent, has a special pharmacotherapeutic profile (long action, good postoperative analgetic effect), that makes it particularly suitable for the application in oral implantology providing better blood circulation at the implant placement sites than other anesthetics, thus ensuring better conditions for good osseointegration, especially within the first 48 h after the placement of implants 21 .Being produced in our country, makes it available for a wide everyday use in clinical practice.Regarding bupivacaine, however, a number of authors think that its application without vasoconstrictor does not meet the requirements for the assessment of the efficacy of a local anesthetic solution 20−22 .Oral implants placement procedures could last several hours, during which we have to obtain effective local anesthesia and good blood circulation at the implant placement sites.The presence of vasoconstrictor in bupivacaine solution is important for the achivement of effective local anesthesia, but could compromise dental implant sites blood circulation.Thus, the aim of this study was to determine and, then, to compare clinical parameters of the local anesthetic effects of bupivacaine applied, firstly, with and, secondly, without the addition of a vasoconstrictor in the placement of endosseous B.C.T. implants.

Methods
The Ethical Committee in Human Research in the Military Medical Academy, Belgrade, approved this investigation and written consent was obtained from each of the patients.This investigation included 30 randomly selected patients of both sexes, who ranged in age from 30−60 years, with partially or totally edentulous mandible, and all of them complied with any elements of dentistry and general medicine indications and contraindications.These patients, scheduled for dental implantation placement, were asked to participate in the study.Firstly, the patients were subjected to local anesthesia with 3.5 cm 3 of 0.5% bupivacaine with a vasoconstrictor (adrenalin, 1: 200 000) in the right side of the mandible.After administering local anesthesia, the placement of B.C.T. im-plants was performed.Secondly, after 7−10-day period from the first intervention, the patients were subjected to local anesthesia with 3.5 cm 3 of 0.5% bupivacaine, but without a vasoconstrictor in the left side of the mandible.After administering local anesthesia, the placement of B.C.T. implants was performed.During the performance of both oral surgery procedures, the clinical parameters of the local anesthetic effects were evaluated as follows: the onset of anesthesia -latent period (occurrence of lower lip numbness); potency of anesthesia during intervention graded as A (insensibility of the lower lip and tangue), B (preassure, no pain in the implant site region), C (moderate bearable pain in the implant site regin), and D (intense pain in the implant site region requering additional anesthesia); duration of soft tissue anesthesia -the patients were asked to grade it according to the cessation of soft tissue numbness; intensity of postoperative pain on a visual analog scale (VAS) questionnaire.On the 10-point VAS, 0 represented no pain, whereas 10 marked the highest score.All the patients marked their subjective response to postoperative pain on a VAS (Fig. 1).Statistical analysis was performed by determining the following parameters: mean values, standard deviation, standard errors, statistical significance of differences in mean values.The Student's t test and χ 2 test were used to determine a statistical significance of the differences in mean value .

Results
The results obtained by examining the latent period after administering local anesthesia with bupivacaine with and without vasoconstrictor are shown in Table 1.
The onset of anesthesia after applying bupivacaine without vasoconstrictor was 6 min, while with the addition of vasoconstrictor it was 5 min.It was statistically significantly longer latent period in anesthesia with bupivacaine without vasoconstrictor (6±2 : 5±2, p < 0.05).
The potency of soft tissue anesthesia after applying bupivacaine with and without vasoconstrictor was good.No pain was experienced by 14 of the patients (53%), and pressure without pain in 12 of the patients (37%).A sense of moderate pain was registered in 6 of the patients (20%).The data referring to the potency of anesthesia are shown in Table 2.
Statistical analysis of the obtained results for the potency of anesthesia showed no significant difference in the frequency of distribution of the potency of local anesthesia with bupivacaine without vasoconstrictor in regard to theoretical distribution, while there was a significant difference in the frequency of distribution of the potency of local anesthesia with bupivacaine with vasoconstrictor in regard to theoretical distribution (p < 0.05).However, comparison between differences of proportions of the potency of local anesthesia with and without vasoconstrictor did not show any statistical significance.
The results obtained by testing the duration of local anesthesia after applying bupivacaine with and without vasoconstrictor are shown in Table 3.
The duration of local anesthesia after applying bupivacaine with vasoconstrictor was in averrage 369 min, while it was 440 min without the addition of vasoconstrictor.There was no statistical difference between these values, yet they befell in the border of statistical significance (p = 0.0779 for the possibility of 95%).
The results of the assessment of postoperative pain (analgetic effect) of local anesthetic with and without vasoconstrictor are shown in Table 4.The results obtained by the assessmenet of bupivacaine analgetic effect show that the percentage of patients with the lowest subjective sensation of analgetic activity was higher with bupivacaine without vasoconstrictor (76% of the patients with the score 1 on a visual analog scale).No statistically significant differences were found between the proportions of postoperative analgetic effect in anesthesia with bupivacaine applied with or without vasoconstrictor.

Discussion
Regarding bupivacaine, a number of authors think that its application without vasoconstrictor does not meet the requirements for the assessment of the efficacy of a local anesthetic solution 20 .Oral implants placement procedures could last several hours, during which we have to obtain effective local anesthesia and good blood circulation at the implant placement sites.The presence of a vasoconstrictor in bupivacaine solution is important for the achievement of effective local anesthesia, but could compromise dental implant sites blood circulation.Bupivacaine, a long-acting agent, has rapidly become a standard part of the instrumentarium for postsurgical pain control ever since its introduction to the dental local anesthesia in 1983 21,22 .The major advantage of its use is the long duration of its anesthetic effect, with a very slow return to full sensation, which eases patient through the early postoperative period 21 .Bupivacaine provides a significantly great duration of anesthesia, decreased postoperative pain, and a reduction in the amount of analgetics taken 23,24 .Regarding addition of a vasoconstrictor to a local anesthetic it can have both beneficial and detrimental effects.Among the beneficial ones are: a decrease in the plasma peak concentration of the local anesthetic agent, increase in the duration and the quality of anesthesia, reduction of the minimum concentration of anesthetic needed for nerve block, and decrease of blood loss during surgical procedures.The addition of a vasoconstrictor to a local anesthetic may also have detrimental effects, the major among them being that it could compromise dental implant sites blood circulation, and that it is not always optimal to achieve the purposes for which it is added 17 .The present study evaluated and compared local anesthesia with bupivacaine both with and without vasoconstrictor.The obtained results indicated that the latent period observed for bupivacaine without vasoconstrictor was statistically significantly longer (6 min 23 sec) than with it.Similar results in regard with the duration of latent period have been obtained by other investigators reporting even 8 min for mandibular anesthesia 25 .
The results obtained for the potency of local anesthesia did not differ for both solutions.There was no need for additional anesthesia.This slightly differs from the results of other authors 22,25,26 , since in our study we used 3.5 cm 3 of 0.5% local anesthetics, which could provide a sufficient quantity of the anesthetic for mandibular anesthesia in placement B.C.T. implants.
With respect to the duration of local anesthesia, there was no significant difference observed between the solutions, but it remains to note the fact that it was slightly longer without vasoconstrictor (440±212 min).The highest percentage of the patients with the lowest grade for postoperative pain was in the case of bupivacaine administered without vasoconstrictor 27 .This speaks in favour of the wide use of bupivacaine in oral surgery, especially for time-consuming surgical interventions after which postoperative pain could occur 13,14,21 .

Conclusion
The latent period observed for local anesthesia with 3.5 cm 3 of 0.5% bupivacaine plus vasoconstrictor in this study was statistically significantly shorter than that observed for local anesthesia with the same local anesthetic but without vasoconstrictor.The duration of anesthesia observed for bupivacaine without vasoconstrictor was longer than that observed for the drug with vasoconstrictor, while there was no difference in the potency of anesthesia regardless of whether bupivacaine was used with or without vasoconstrictor.The lowest score values for postoperative pain were recorded for bupivacaine without vasoconstrictor.These findings suggest that bupivacaine without vasoconstrictor is efficient for local block anesthesia in placing B.C.T. implants.In this study we also concluded that bupivacaine without a vasoconstrictor provides better blood circulation during dental implants placement which is one of the major preconditions for better implants osseointegration.