Anesthetic efficacy and heart rate effects of the supplemental intraosseous injection of 2% mepivacaine with 1:20,000 levonordefrin

Vol. 87 No. 3 March 1999

ORAL SURGERY, ORAL MEDICINE, ORAL PATHOLOGY,

ORAL AND MAXILLOFACIAL SURGERY

Editor: Larry J. Peterson

Anesthetic efficacy and heart rate effects of the supplemental intraosseous injection of 2% mepivacaine with 1:20,000 levonordefrin Anna Guglielmo, DDS, MS,a Al Reader, DDS, MS,b Robert Nist, DDS, MS,c Mike Beck, DDS, MA,d and Joel Weaver, DDS, PhD,e Columbus, Ohio THE OHIO STATE UNIVERSITY

Objective. The purpose of this study was to determine the anesthetic efficacy and heart rate effects of a supplemental intraosseous injection of 2% mepivacaine with 1:20,000 levonordefrin.

Study design. Through use of a repeated-measures design, 40 subjects randomly received 3 combinations of injections at 3 separate appointments. The combinations were as follows: inferior alveolar nerve (IAN) block (with 3% mepivacaine) + intraosseous injection of 1.8 mL of 2% mepivacaine with 1:20,000 levonordefrin; IAN block + intraosseous injection of 1.8 mL of 2% lidocaine with 1:100,000 epinephrine (positive control); IAN block + mock intraosseous injection (negative control). Each first molar, second molar, and second premolar was blindly tested with a pulp tester at 2-minute cycles for 60 minutes after injection. Anesthesia was considered successful when 2 consecutive readings of 80 were obtained. Heart rate (pulse rate) was measured with a pulse oximeter. Results. One hundred percent of the subjects had lip numbness with the IAN block + intraosseous mock technique and IAN block + intraosseous techniques. The anesthetic success rates for IAN block + mock intraosseous injection, IAN block + intraosseous lidocaine, and IAN block + intraosseous mepivacaine, respectively, were as follows: 80%, 100%, and 100% for the first molar; 90%, 100%, and 100% for the second molar; 77%, 97%, and 97% for the second premolar. For the first molar and second premolar, the differences were significant (P < .05) when the intraosseous mepivacaine and lidocaine techniques were compared with the IAN block + mock intraosseous injection. There were no significant differences between the intraosseous mepivacaine and lidocaine techniques. Eighty percent of the subjects had a mean increase in heart rate of 23-24 beats per minute with the intraosseous injection of the mepivacaine and lidocaine solutions; there were no significant differences between results with the 2 solutions. Conclusions. We concluded that intraosseous injection of 1.8 mL of 2% lidocaine with 1:100,000 epinephrine or 2% mepivacaine with 1:20,000 levonordefrin, used to supplement an IAN block, significantly increased anesthetic success in first molars and second premolars. The 2 solutions were equivalent with regard to intraosseous anesthetic success rate, failure rate, and heart rate increase after IAN block.

(Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1999;87:284-93)

The Stabident intraosseous (IO) injection system allows placement of a local anesthetic directly into the cancelThis study was supported by Graduate Endodontic Research Funds and The Steven Goldberg Memorial Fund. aFormer Graduate Student in Endodontics. bProfessor and Program Director, Graduate Endodontics. cFormer Associate Clinical Professor, Division of Endodontics. dAssociate Professor, Department of Health Services Research. eAssociate Professor, Department of Oral and Maxillofacial Surgery, Oral Pathology, Anesthesiology. Received for publication July 27, 1998; returned for revision Oct 7, 1998; accepted for publication Nov 12, 1998. Copyright © 1999 by Mosby, Inc. 1079-2104/99/$8.00 + 0 7/12/95975

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lous bone adjacent to a tooth to be anesthetized. This system has been evaluated both as a primary injection and as a supplemental injection. Leonard1 reported that most extractions were successful with this system. Coggins et al2 used the Stabident IO system as a primary injection in various groups of maxillary and mandibular teeth; they reported a success rate of 75% for the mandibular first molar. Replogle et al3 reported that a primary IO injection of 2% lidocaine with 1:100,000 epinephrine was more successful and resulted in a longer duration of pulpal anesthesia than a primary injection of 3% mepivacaine in mandibular first molars. Dunbar et al4 evaluated the Stabident IO system in mandibular first

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Table I. Percentages and discomfort ratings for infiltration and IO injections Injection phase Infiltration injection Needle insertion Mock Lidocaine Mepivacaine Solution deposition Mock (3% mepivacaine) Lidocaine Mepivacaine IO technique Perforation Mock IO Lidocaine Mepivacaine Solution deposition Mock IO Lidocaine Mepivacaine

None

Mild

Moderate

Severe

35% (14/40) 50% (20/40) 43% (17/40)

57% (23/40) 47% (19/40) 57% (23/40)

7% (3/40) 3% (1/40) 0% (0/40)

0% (0/40) 0% (0/40) 0% (0/40)

77% (31/40) 90% (36/40) 90% (36/40)

23% (9/40) 10% (4/40) 10% (4/40)

0% (0/40) 0% (0/40) 0% (0/40)

0% (0/40) 0% (0/40) 0% (0/40)

95% (38/40) 70% (28/40) 75% (30/40)

5% (2/40) 25% (10/40) 20% (8/40)

0% (0/40) 5% (2/40) 5% (2/40)

0% (0/40) 0% (0/40) 0% (0/40)

100% (40/40) 67% (27/40) 73% (29/40)

0% (0/40) 25% (10/40) 20% ( 8/40)

0% (0/40) 7% (3/40) 5% (2/40)

0% (0/40) 0% (0/40) 3% (1/40)

molars as a supplement to the inferior alveolar nerve (IAN) block; they recorded a high incidence of pulpal anesthesia (100%), with 90% of the first molars still anesthetized at 60 minutes. In a clinical study, Nusstein et al5 found that a supplemental mandibular IO injection of 1.8 mL of 2% lidocaine with 1:100,000 epinephrine was 90% successful in gaining total pulpal anesthesia for teeth diagnosed with irreversible pulpitis. Reisman et al6 reported that the supplemental IO injection of 1.8 mL of 3% mepivacaine increased success in mandibular teeth diagnosed with irreversible pulpitis to 80% in comparison with the IAN block alone (which was associated with a 25% success rate). A repeated IO injection of 3% mepivacaine increased success to 98%. Coggins et al,2 Replogle et al,3 and Dunbar et al4 all used an IO injection site distal to the first molar and 1.8 mL of anesthetic solution. Reitz et al7 used an IO injection site distal to the second premolar and 0.9 mL of 2% lidocaine with 1:100,000 epinephrine intraosseously after an IAN block; they found that the incidence of anesthesia was significantly increased in the second premolar (for 50 minutes) and first molar (for 20 minutes) in comparison with the incidence for the IAN block alone. In each of the aforementioned studies in which a solution containing a vasoconstrictor was selected, epinephrine was used. Levonordefrin is the major alternative to epinephrine in the United States. No objective study has evaluated the Stabident IO technique using a solution containing the alternative vasoconstrictor levonordefrin. The purpose of our study was to determine the anesthetic efficacy and heart rate effects of a supplemental IO injection of 2% mepivacaine with 1:20,000 levonordefrin. Injection pain and postoperative healing were also assessed for the IO injections.

MATERIAL AND METHODS Forty adult subjects participated; 26 of them were male and 14 were female. The subjects ranged in age from 20 to 40 years; the average age was 26 years. All subjects were in good health, and none were taking any medications that would alter pain perception. The study was approved by The Ohio State University Human Subjects Review Committee; written informed consent was obtained from each subject. Equal numbers of mandibular right and left sides were tested, with the first molar, second molar, and second premolar chosen as the test teeth. The contralateral canine was used as the unanesthetized control to ensure that the pulp tester was operating properly and that the subject was responding appropriately during the experiment. Clinical examinations indicated that all teeth were free of caries, large restorations, and periodontal disease; none had histories of trauma or sensitivity. Three appointments at least 2 weeks apart were scheduled for each of the 40 subjects. With a repeatedmeasures design, each subject received (1) a combination IAN block (with 1.8 mL of 3% mepivacaine) plus IO injection of 1.8 mL of 2% mepivacaine with 1:20,000 levonordefrin (2% Carbocaine with Neo-Cobefrin, Cook-Waite, New York, NY), (2) a combination IAN block plus IO injection of 1.8 mL of 2% lidocaine with 1:100,000 epinephrine (positive control; Xylocaine, Astra Pharmaceutical Inc, Westborough, Mass), and a combination IAN block plus mock IO injection (negative control). To allow for healing of the perforation site between appointments, the first and third appointments were randomized with respect to whether the subject received the combination IAN block + IO injection of 2% lidocaine with 1:100,000 epinephrine or the combi-

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Table II. Percentages and numbers of subjects who experienced anesthetic success and failure (n = 40) Outcome

Tooth

IAN block + mock IO injection

IAN block + IO lidocaine

IAN block + IO mepivacaine

First molar Second molar Second premolar

80% (32/40) 90% (36/40) 77% (31/40)

100% (40/40)* 100% (40/40) 97% (39/40)*

100% (40/40)*† 100% (40/40)† 97% (39/40)*†

First molar Second molar Second premolar

20% (8/40) 10% (4/40) 23% (9/40)

0% (0/40)* 0% (0/40) 3% (1/40)*

0% (0/40)*† 0% (0/40)† 3% (1/40)*†

Anesthetic success

Anesthetic failure

*Significantly different when IAN block + mock IO injection was compared with IAN block + IO lidocaine or IAN block + IO mepivacaine (P < .05). †No significant difference between IAN block + IO lidocaine and IAN block + IO mepivacaine (P > .05).

nation IAN block + IO injection of 2% mepivacaine with 1:20,000 levonordefrin; the second appointment was always the combination IAN block + mock IO injection. Therefore, at least 4 weeks always separated the actual IO injections. All IAN blocks and IO injections were given by the principal investigator (A.G.). So that the operator and the subject would be effectively blinded to the anesthetic solutions administered, each anesthetic cartridge (mepivacaine or lidocaine) was masked with a white opaque label and numbered to determine the order of anesthetic administration. A trained assistant loaded each syringe before the appointment. At the beginning of each appointment and before any injections were given, the experimental teeth and control canine were tested 3 times with a pulp tester (Analytic Technology Corp., Redmond, Wash) to record baseline vitality. After the tooth to be tested was isolated with cotton rolls and dried with gauze, toothpaste was applied to the probe tip, which was then placed midway between the gingival margin and the occlusal edge of the tooth. The current rate was set at 25 seconds to increase from no output (0) to the maximum output (80). The number at initial sensation was recorded. All preinjection and postinjection tests were performed by trained personnel who were blinded to the IO or mock IO injections administered. The standard IAN block was administered with a 27gauge 11⁄2-inch needle (Monoject, Sherwood Medical, St Louis, Mo) through use of 1.8 mL of 3% mepivacaine plain (3% Polocaine, Astra Pharmaceutical Products Inc). After the target area was reached and aspiration was performed, the solution was deposited over a period of 1 minute. The IO injection was administered 5 minutes after completion of the IAN block if subjective lip numbness was recorded by the subject. Every minute for 5 minutes, the subject was asked, “Is your lip numb?” If lip numbness did not occur within 5 minutes, the subject was reappointed. McLean et al8 found the mean onset of lip

numbness to be 5 minutes for the IAN block, and this time was used for the onset of lip numbness. All subjects had profound lip numbness after the IAN block. Mucosal sticks could have been used to determine success of the IAN block; previous studies8-10 demonstrated that 90% to 100% of patients felt no response to mucosal sticks in the distribution of the mental nerve after receiving an IAN block. However, the percentage of patients with pulpal anesthesia, as measured with the electric pulp tester, was much lower, which is similar to the findings of our study. Therefore, mucosal sticks are not an objective indicator of the success of an IAN block or of pulpal anesthesia. The IO injection was given by means of the Stabident system (Fairfax Dental Inc, Miami, Fla). With the subject in a reclining position, the area of perforation was determined according to a horizontal line along the buccal gingival margins of the first and second molars and a vertical line that passed through the interdental papilla on the distal aspect of the first molar. A point approximately 2 mm below the intersection of these lines was selected as the perforation site if the site was in attached gingiva; if this point was in alveolar mucosa (as was the case in 3 subjects), the injection site was moved to just above the junction of the attached gingiva and alveolar mucosa. The soft tissue at the determined perforation site was anesthetized with an infiltration injection of approximately 0.1 mL of the mepivacaine solution or the lidocaine solution (deposited through an ultra-short Stabident needle). For the mock injection, 0.1 mL of 3% mepivacaine was used for the infiltration injection. The cortical bone was perforated with the Stabident perforator (a beveled-ended solid wire attached to a plastic hub) in a contra-angle, slow-speed handpiece. The perforator was placed through the gingiva at the infiltration site and oriented perpendicular to the cortical plate. With the point gently resting against bone, the handpiece was activated in a series of short bursts, using light pressure, until a “breakthrough” feeling was observed or until 2 to 5 seconds had elapsed. For the mock perforation, the perfo-

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Fig 1. Incidence of first molar anesthesia as determined by lack of response to electric pulp testing at maximal setting (percentage of 80 readings) at each postinjection time interval for 3 injection techniques. Significant differences (P < .05) between IAN block, IAN block + IO (lidocaine) and IAN block + IO (mepivacaine) are indicated (asterisk and cross, respectively).

rator was placed through the gingiva only and then withdrawn; the handpiece was then activated for 2 to 5 seconds but there was no contact with tissue. Before insertion of the 27-gauge ultra-short Stabident needle through the perforation, the needle was bent at the hub to a 45-degree angle to allow for ease of insertion. The area of perforation was blotted with a sterile cotton roll to control hemorrhage and identify the perforation site (a small dot of hemorrhage on the blanched gingiva). The standard syringe was held in a pen-gripping fashion, the needle was inserted into the perforation site, and 1.8 mL of either 2% lidocaine with 1:100,000 epinephrine or 2% mepivacaine with 1:20,000 levonordefrin was delivered over a 2-minute time period. The mock IO injection was performed in a similar manner, except that no anesthetic solution was deposited. The length of time for the mock IO injection was identical to that for the actual IO injection. In addition, each subject was instructed to close his or her eyes during all injections to ensure blinding to the techniques. The pulp-testing personnel were not present during the IO injections. The subjects were instructed to rate the pain of the infiltration and IO injections. The rating scale was as follows: 0, no pain; 1, mild pain (pain that is recognizable but not discomforting); 2, moderate pain (pain that is discomforting but bearable); 3, severe pain (pain that causes considerable discomfort and is difficult to bear). At 1 minute after the IO injection (9 minutes after completion of the IAN block), the first and second molars were pulp-tested. At 2 minutes, the second premolar and contralateral control canine were tested.

This cycle of testing was repeated every 2 minutes. The control canine was tested every 6 minutes with an inactive pulp tester to test the reliability of the subjects. All testing was stopped at 60 minutes after IO injection. Lack of response by the subject to the maximum output of the pulp tester (a reading of 80) was used as the criterion for pulpal anesthesia. Anesthesia was considered successful when 2 consecutive readings of 80 were obtained. Anesthesia was considered a failure if the subject never achieved 2 consecutive readings of 80. To monitor the heart rate (pulse rate), the subjects were connected to a pulse oximeter (Criticare Systems Inc, Waukesha, Wis) by means of a sensor that was attached to the nail of a forefinger. Altemeyer et al11 found pulse oximetry to be accurate in comparison with heart rate recordings from electrocardiograms. Through use of an automated printout, heart rate was recorded before and during the IO injection and for 30 minutes thereafter. After placement of the sensor and verification of adequate function, the subject sat quietly in a reclining position for 8 minutes. For purposes of data analysis, readings were grouped into 4 time periods. Period 1 (baseline recordings) was the average of readings taken at 2-minute intervals during initial electric pulp testing, IAN block, infiltration, and perforation. Period 2 was the average of 8 sets of readings taken at 15-second intervals during anesthetic solution IO deposition. Period 3 was the average of 8 sets of readings taken at 15-second intervals for 2 minutes after deposition; 2 minutes after deposition, the subject was asked, “Did your heart feel as if it were beating rapidly?” Period 4 was the average of 14

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Fig 2. Incidence of second molar anesthesia, as determined by lack of response to electric pulp testing at maximal setting (percentage of 80 readings) at each postinjection time interval, for 3 injection techniques. There were no significant differences (P > .05) between IAN block and IAN block + IO (lidocaine or mepivacaine).

sets of readings taken at 2-minute intervals for 30 minutes after deposition. Monitoring of the pulse oximeter was performed by trained assistants who were blinded to the anesthetic solutions administered. A written questionnaire was given to each subject after each injection; it asked the subject to rate the pain (and any side effects) in the area of the IO injection at the time initial numbness wore off and each morning for 3 days after the appointment. The subjects used the same pain rating scale (none, mild, moderate, severe) that was used for rating the pain of the IO injections. For the heart rate, mean values for the pulse rate recordings were analyzed through use of a factorial, repeated-measures analysis of variance. Post hoc testing was done through use of the Tukey procedure. Comparisons were considered significant at P < .05. Comparisons between the IAN block + mock IO injection and the IAN block + IO injections for anesthetic success and failure were analyzed non-parametrically through use of Bonferroni-adjusted McNemar tests. Between-technique comparisons at each 10-minute period for the percentage of pulpal anesthesia (readings of 80) were analyzed through use of Bonferroni-adjusted Wilcoxon signed-ranks tests. Comparisons were considered significant at P < .05.

RESULTS The discomfort ratings for infiltration and solution deposition of the IO and mock IO injections are presented in Table I. Most of the ratings were in the none and mild categories. No perforators broke during the study.

One hundred percent of the subjects had profound lip numbness with the IAN block + mock IO and IAN block + IO injection techniques. Anesthetic success and failure rates are presented in Table II. Anesthetic success for the IAN block + mock IO injection, the IAN block + IO lidocaine, and the IAN block + IO mepivacaine, respectively, were as follows: 80%, 100%, and 100% for the first molar; 90%, 100%, and 100% for the second molar; and 77%, 97%, and 97% for the second premolar. Significant differences (P < .05) were shown for the first molar and second premolar between the IAN block and the combination IAN block + IO injections. There were no significant differences between the combination IAN block + IO lidocaine injections and the combination IAN block + IO mepivacaine injections (Table II and Figs 1 and 3). Anesthetic failure was significantly different between the IAN block + mock IO injection and IAN block + IO injections (with lidocaine and mepivacaine solutions) for the first molars and second premolars. There were no significant differences in heart rate at baseline (period 1) or for 30 minutes postdeposition (period 4) between the solutions and the mock injection. During IO deposition and for 2 minutes postdeposition (periods 2 and 3), 2% mepivacaine (with 1:20,000 levonordefrin) and 2% lidocaine (with 1:100,000 epinephrine) had significantly (P < .05) higher heart (pulse) rate recordings than the mock injection (Table III). There was no significant differences (P > .05) in heart rates between the 2 solutions during these time periods. Thirty-two (80%) of 40 subjects experienced a heart rate increase that may be

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Table III. Pulse rate increase during IO solution deposition and for 2 minutes after deposition (n = 32) Solution Highest mean pulse rate (range) Mean increase (range)

2% mepivacaine (with 1:20,000 lev)* 79 BPM (60-115) 23 BPM (7-47)

2% lidocaine (with 1:100,000 epi)*† 80 BPM (66-120) 24 BPM (7-48)

Mock 69 BPM (62-100) 4 BPM (0-20)

lev, Levonordefrin; epi, epinephrine; BPM, beats per minute. *Significantly different when mepivacaine or lidocaine was compared with mock injection (P < .05). †No significant difference between mepivacaine and lidocaine (P > .05).

attributable to the effect of injected epinephrine or levonordefrin (highest readings recorded during deposition or for 2 minutes postdeposition). The highest mean heart rate recordings for the 3 injections are outlined in Table III. Twenty-seven (84%) of 32 subjects for the mepivacaine solution and 28 (87%) of 32 subjects for the lidocaine solution had their heart rates return to within 5 beats of baseline within 4 minutes after solution deposition. Five (16%) of 32 subjects in the mepivacaine group and 4 (13%) of 32 subjects in the lidocaine group took longer than 4 minutes to return to within 5 beats of baseline (taking up to 6 minutes). In response to questioning, 73% of the subjects reported perception of an increase in heart rate with the IO injection of 2% mepivacaine with 1:20,000 levonordefrin, whereas 78% of the subjects reported perception of such an increase with the IO injection of 2% lidocaine with 1:100,000 epinephrine. The postinjection discomfort ratings for the IO injections are presented in Table IV. Most of the ratings were in the none and mild categories.

DISCUSSION The use of the 80 reading as a criterion for pulpal anesthesia was based on the studies of Dreven et al12 and Certosimo and Archer.13 These studies12,13 showed that an 80 reading ensures pulpal anesthesia in vital asymptomatic teeth. In addition, Certosimo and Archer13 demonstrated that electric pulp testing readings less than 80 resulted in pain during operative procedures in asymptomatic patients. The use of 3% mepivacaine for the IAN block was chosen so that any heart rate effect related to a vasoconstrictor could be attributed to the solution given intraosseously. On the basis of studies by McLean et al8 and Cohen et al,14 there would be no difference in success of the IAN block if 3% mepivacaine or 2% lidocaine with 1:100,000 epinephrine were used. Anesthetic failure with the IAN block occurred in 20% of the first molars, 10% of the second molars, and 23% of the second premolars (Table II). The failure rates are similar to those found in previous studies4,7,8-10,15-17 in which a similar method was used. Therefore, even after a “clinically successful” block (lip numbness), pulpal anesthesia may not be guaranteed. Factors associ-

ated with anesthetic failure for the IAN block have included accessory innervation,18,19 accuracy of needle placement,20,21 anxiety, and psychologic factors.22 The addition of the IO injection to the IAN block was based on the studies of Coggins et al,2 Replogle et al,3 and Dunbar et al.4 Coggins et al2 and Replogle et al3 found that when an IO injection of 1.8 mL of 2% lidocaine with 1:100,000 epinephrine was used as a primary injection, the result was a 75% success rate in mandibular first molars. The same investigators2,3 also reported that the duration of IO anesthesia declined steadily during the first hour. The IO injection could be used as a primary method when only a short duration of anesthesia is required, as shown by Leonard1 for extractions; however, in operative and restorative procedures of 60 minutes’ duration, the true value of the IO injection may be in its use as a supplemental injection.4 Dunbar et al4 evaluated a distal IO injection of 1.8 mL of 2% lidocaine with 1:100,000 epinephrine in mandibular first molars as a supplement to the IAN block. They recorded a high incidence of pulpal anesthesia (100%), with 90% of the first molars still anesthetized at 60 minutes. Onset of pulpal anesthesia (highest percentage of initial readings of 80) was fairly rapid with the IO injection of mepivacaine and lidocaine (Figs 1 and 2). Dunbar et al4 and Reitz et al7 also reported that the addition of the IO injection after the IAN block resulted in a fairly quick onset of pulpal anesthesia. For both of the IAN block + IO injection combinations, anesthetic success was 100% for the first molar, with approximately 90% (mepivacaine solution) and 85% (lidocaine solution) of first molars still anesthetized at 60 minutes (Table II and Fig 1). In comparison with IAN block + mock IO injection, the IAN block + IO injection anesthetic success rates were statistically significant (P < .05; Table II), with significant differences shown for the incidence of pulpal anesthesia at 9 through 60 minutes for the mepivacaine solution and at 9 through 60 minutes for the lidocaine solution. Therefore, the addition of the IO injections increased success in the first molar in comparison with the IAN block alone. Dunbar et al4 reported similar results for the first molar using an identical method. There were no significant differences in success rates

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Fig 3. Incidence of second premolar anesthesia, as detemined by lack of response to electric pulp testing at maximal setting (percentage of 80 readings) at each postinjection time interval, for 3 injection techniques. Significant differences (P < .05) between IAN block, IAN block + IO lidocaine, and IAN block + IO mepivacaine are indicated (asterisk and cross, respectively).

between the combination IAN block + IO injection of 2% lidocaine with 1:100,000 epinephrine and the combination IAN block + IO injection of 2% mepivacaine with 1:20,000 levonordefrin. Therefore, the solutions are equivalent in success rates and duration of anesthesia in mandibular first molars when used in IO injections to augment an IAN block. For both of the IAN block + IO injection combinations, anesthetic success was 100% for the second molar, with approximately 95% to 98% of the second molars still anesthetized at 60 minutes (Table II and Fig 2). In comparison with IAN block + mock IO injection, the IAN block + IO injection anesthetic success rates for the lidocaine and mepivacaine solutions were not statistically significant (P > .05; Table II). The most likely reason for the lack of significance was the high success rate of the initial IAN injection; the increase in pulpal anesthesia with the IO injections did not statistically increase the success rate in the second molar. For both of the IAN block + IO injection combinations, anesthetic success was 97% for the second premolar, with approximately 60% to 65% of the premolars still anesthetized at 60 minutes (Table II and Fig 3). In comparison with IAN block + mock IO injection, the IAN block + IO injection anesthetic success rates were statistically significant (P < 0.05; Table II), with significant differences shown for the incidence of pulpal anesthesia at 9 through 40 minutes for the lidocaine solution and at 9 through 40 minutes for the mepivacaine solution. Therefore, the addition of the IO injections increased success in the second premolar in comaprison with the IAN block alone. The duration of pulpal anesthesia with

the IO injections in the second premolar was less than in the first molar (Figs 2 and 3). This has also been reported by Dunbar et al.4 The mostly likely reason for this finding is the use of an IO injection site distal to the first molar, which decreased the amount of anesthetic available to the second premolar. There were no significant differences in success rates between the comination IAN block + IO injection of 2% lidocaine with 1:100,000 epinephrine and the combination IAN block + IO injection of 2% mepivacaine with 1:20,000 levonordefrin. Therefore, the solutions are equivalent in success rates and duration of anesthesia in mandibular second premolars when used in IO injections to augment an IAN block. Anesthetic failure with the combination IAN block + IO injections were 0% for the first molar, 0% for the second molar, and 3% for the second premolar (Table II). The difference between the IAN block + mock IO injection and IAN block + IO injection combinations was statistically significant (P < 0.05) for the first molars and second premolars. Because of the lower failure rate with the initial IAN block, no differences were shown for the second molar (Table II). Clinically, the addition of the IO injection of 2% lidocaine with 1:100,000 epinephrine or 2% mepivacaine with 1:20,000 levonordefrin as used in this study to augment the IAN block will decrease anesthetic failure in the first molar and second premolar. However, it may be preferable to use an IO injection site distal to the second premolar to further decrease the anesthetic failure rate for the second premolar, as shown by Reitz et al.7 Although few comparative studies have been performed, Weil et al23 concluded that 2% mepivacaine

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Table IV. Summary of pain ratings from postinjection surveys on IO injections Pain rating Day 0* Mock IO Lidocaine Mepivacaine Day 1 Mock IO Lidocaine Mepivacaine Day 2 Mock IO Lidocaine Mepivacaine Day 3 Mock IO Lidocaine Mepivacaine

None (0)

Mild (1)

Moderate (2)

Severe (3)

67% (27/40) 57% (23/40) 55% (22/40)

30% (12/40) 35% (14/40) 35% (14/40)

3% (1/40) 7% (3/40) 7% (3/40)

0% (0/40) 0% (0/40) 3% (1/40)

90% (36/40) 37% (15/40) 57% (23/40)

7% ( 3/40) 53% (21/40) 30% (12/40)

3% (1/40) 10% (4/40) 10% (4/40)

0% (0/40) 0% (0/40) 3% (1/40)

97% (39/40) 60% (24/40) 90% (36/40)

3% (1/40) 37% (15/40) 7% (3/40)

0% (0/40) 3% (1/40) 3% (1/40)

0% (0/40) 0% (0/40) 0% (0/40)

100% (40/40) 80% (32/40) 97% (39/40)

0% (0/40) 17% (7/40) 3% (1/40)

0% (0/40) 3% (1/40) 0% (0/40)

0% (0/40) 0% (0/40) 0% (0/40)

*Rating at time subjective numbness wore off.

with 1:20,000 levonordefrin was clinically similar to 2% lidocaine with 1:100,000 epinephrine in operative procedures. In an experimental study, Hinkley et al10 found the 2 solutions to be equivalent in an IAN block. The results of the current study indicate they are also equivalent for supplemental IO injections in mandibular posterior teeth. The infiltration and IO injections resulted in low pain ratings, with a few reports of moderate or severe pain (Table I). The low ratings were probably due to the anesthesia provided by the IAN block and infiltration injection. Similar results for the supplemental IO injection after IAN block have been reported by Dunbar et al4 and Reitz et al.7 Therefore, the infiltration and IO injections after IAN block have a fairly low potential for moderate or severe pain. Postinjection pain for the IO injections was rated as none to mild at the time subjective numbness wore off in 90% of the IO injections with the mepivacaine solution and in 93% of the IO injections with the lidocaine solution; 0% to 7% of subjects reported moderate or severe pain (Table III). In general, the pain ratings decreased over the next 3 days. Various postinjection pain ratings have been reported: Dunbar et al, 4 2% moderate pain; Coggins et al,2 2% to 15% moderate pain; Replogle et al,3 2% to 5% moderate pain; Reitz et al,7 11% moderate pain. Therefore, the IO injection has a 2% to 15% potential for moderate postinjection pain. Various authors2-5,7 have reported a transient increase in heart rate (46% to 85% of the time) with Stabident IO injection of epinephrine-containing solutions. In our study, 78% (31/40) of the subjects receiving the lidocaine solution and 73% (29/40) of the subjects receiving the mepivacaine solution reported perception of an increase in heart rate (in response to subject questioning) during

solution deposition or for 2 minutes after the IO injection; these percentages compared with 0% for the mock IO injection. As measured objectively with the pulse oximeter, the highest heart rate for 80% (32/40) of the subjects occurred during deposition or for 2 minutes after deposition of the mepivacaine and lidocaine solutions. The subjective questioning and objective recording were similar; this has also been reported by Replogle et al.24 Replogle et al24 found that 67% of their subjects objectively (according to electrocardiogram recordings) had increased heart rates with the IO injection of 1.8 mL of 2% lidocaine with 1:100,000 epinephrine; the mean increase was 28 beats per minute. Our study recorded a greater percentage of subjects with an increase (80%), but the mean increase in beats per minute was similar (23 to 24 beats). It may be that our population was slightly more sensitive to the effects of epinephrine than the population studied by Replogle et al.24 In 84% of our subjects receiving 2% mepivacaine with 1:20,000 levonordefrin and in 87% of our subjects receiving 2% lidocaine with 1:100,000 epinephrine, the heart rate returned to within 5 beats of baseline by 4 minutes after solution deposition. In 5 subjects (16%) who received mepivacaine and 4 subjects (13%) who received lidocaine, the return took up to 6 minutes. Using 2% lidocaine with 1:100,000 epinephrine, Replogle et al24 found that whereas 79% of their subjects returned to within 5 beats of baseline by 4 minutes, 21% of the subjects took up to 22 minutes. Clinically, it appears that most subjects will report an increased heart rate after the IO injection of either 2% mepivacaine with 1:20,000 levonordefrin or 2% lidocaine with 1:100,000 epinephrine through use of the Stabident system. The heart rate generally returns to near baseline readings within 4 minutes in most patients.

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Although a heart rate increase with the IO injection of 2% mepivacaine (with 1:20,000 levonordefrin) or 2% lidocaine (with 1:100,000 epinephrine) would probably be noticed by the patient, it would not be clinically significant in most healthy people.24 Replogle et al24 discussed the clinical significance, cardiovascular effects, and contraindications to the use of epinephrine in IO injections; the reader is referred to their article for a review. The advertisement for 2% Carbocaine with 1:20,000 Neo-Cobefrin makes the following statement: “Neo-Cobefrin is a vasoconstrictor that produces less cardiac and central nervous system stimulation than epinephrine does.” Although this is basically correct,25,26 levonordefrin is marketed in dentistry in a 5-fold higher concentration (1:20,000) than epinephrine (1:100,000); the benefits of less cardiac stimulation may thus not be realized with this concentration. As pointed out by Robertson et al,27 levonordefrin was similar to epinephrine in its heart rate increase and at low doses was equal in potency to epinephrine in direct pressor effects. Yagiela et al28 and Dreyer and Offermeier,29 giving intravenous injections of levonordefrin in doses similar to that contained in dental local anesthetic preparations, have noted a transient increase in cardiac rate and significant increases in blood pressure. We studied only heart rate, inasmuch as this was the parameter that changed most frequently during IO injections.24 Blood pressure may be equally important with levonordefrin, and future studies might address this parameter. The results of the present study would indicate that IO injection of 2% mepivacaine with 1:20,000 levonordefrin is equivalent to IO injection of 2% lidocaine with 1:100,000 epinephrine in terms of heart rate increase. Although no animal study has investigated the effects of Stabident IO injection on gingiva and bone, Dunbar et al,4 Coggins et al,2 Replogle et al,3 and Reitz et al7 have reported swelling and purulence at Stabident IO injection sites. In general, the incidence in these studies 2-4,7 has been less than 5%. These changes are likely related to gingival or bone trauma during perforation. In the current study, just 2 (3%) of 80 subjects reported postinjection swelling or exudate. Clinically, the chance is small that swelling or exudate will occur postoperatively. Nine percent (7/80) of the subjects who received perforations reported that for a few days the first molar “felt high” during chewing. Other studies2-4,7 in which the Stabident technique was used have reported an incidence of such a feeling of 0% to 13%. This feeling is most likely an increased awareness to biting that results from soreness in the area caused by damage from perforation or inflammation of the bone. No subjects reported symptoms of a pulpal nature postoperatively,

and all subjects who received the IO injection at the first appointment had similar baseline pulp test readings at subsequent appointments. In conclusion, IO injection of 1.8 mL of 2% lidocaine with 1:100,000 epinephrine or 2% mepivacaine with 1:20,000 levonordefrin, when used to supplement an IAN block, significantly increased anesthetic success in the first molars and second premolars. The 2 solutions were equivalent with respect to IO anesthetic success rate, failure rate, and heart rate increases after IAN block. REFERENCES 1. Leonard M. The efficacy of an intraosseous injection system of delivering local anesthetic. J Am Dent Assoc 1995;126:81-6. 2. Coggins R, Reader A, Nist R, Beck M, Meyers W. Anesthetic efficacy of the intraosseous injection in maxillary and mandibular teeth. Oral Surg Oral Med Oral Oral Pathol Oral Radiol Endod 1996;81:634-41. 3. Replogle K, Reader A, Nist R, Beck M, Weaver J, Meyers W. Anesthetic efficacy of the intraosseous injection of 2% lidocaine (1:100,000 epinephrine) and 3% mepivacaine in mandibular first molars. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1997;83:30-7. 4. Dunbar D, Reader A, Nist R, Beck M, Meyers W. Anesthetic efficacy of the intraosseous injection after an inferior alveolar nerve block. Journal of Endodontics 1996;22:481-6. 5. Nusstein J, Reader A, Nist R, Beck M, Meyers WJ. Anesthetic efficacy of the supplemental intraosseous injection of 2% lidocaine with 1:100,000 epinephrine in irreversible pulpitis. Journal of Endodontics 1998;24:487-91. 6. Reisman D, Reader A, Nist R, Beck M, Weaver J. Anesthetic efficacy of the supplemental intraosseous injection of 3% mepivacaine in irreversible pulpitis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1997;84:676-82. 7. Reitz J, Reader A, Nist R, Beck M, Meyers WJ. Anesthetic efficacy of the intraosseous injection of 0.9 ml of 2% lidocaine (1:100,000 epinephrine) to augment an inferior alveolar nerve block. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1998;86:516-23. 8. McLean C, Reader A, Beck M, Meyers WJ. An evaluation of 4% prilocaine and 3% mepivacaine compared to 2% lidocaine (1:100,000 epinephrine) for inferior alveolar nerve block. Journal of Endodontics 1993;19:146-50. 9. Vreeland D, Reader A, Beck M, Meyers W, Weaver J. An evaluation of volumes and concentrations of lidocaine in human inferior alveolar nerve block. Journal of Endodontics 1989;15:6-12. 10. Hinkley S, Reader A, Beck M, Meyers W. An evaluation of 4% prilocaine with 1:200,000 epinephrine and 2% mepivacaine with levonordefrin compared to 2% lidocaine with 1:100,000 epinephrine for inferior alveolar nerve block. Anesthesia Progress 1991;38:84-9. 11. Altemeyer KH, Mayer J, Berg-Seiter S, Fosel T. Pulse oximetry as a continuous, noninvasive monitoring procedure: comparison of two instruments. Anesthesiology 1986;35:43-5. 12. Dreven L, Reader A, Beck M, Meyers W, Weaver J. An evaluation of the electric pulp tester as a measure of analgesia in human vital teeth. Journal of Endodontics 1987;13:233-8. 13. Certosimo A, Archer R. A clinical evaluation of the electric pulp tester as an indicator of local anesthesia. Operative Dentistry 1996;21:25-30. 14. Cohen HP, Cha BY, Spångberg LSW. Endodontic anesthesia in mandibular molars: a clinical study. Journal of Endodontics 1993;19:370-3. 15. Nist R, Reader A, Beck M, Meyers W. An evaluation of the incisive nerve block and combination inferior alveolar and incisive nerve blocks in mandibular anesthesia. Journal of Endodontics 1992;18:455-9.

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16. Childers M, Reader A, Nist R, Beck M, Meyers W. The anesthetic efficacy of the periodontal ligament injection after an inferior alveolar nerve block. Journal of Endodontics 1996;22:317-20. 17. Bou Dagher F, Yared GM, Machtou P. The anesthetic efficacy of volumes of lidocaine in inferior alveolar nerve blocks. Journal of Endodontics 1997;23:178-80. 18. Frommer J, Mele FA, Monroe CW. The possible role of the mylohyoid nerve in mandibular posterior tooth sensation. J Am Dent Assoc 1972;85:113-7. 19. Wilson S, Johns P, Fuller PM. The inferior alveolar and mylohyoid nerves: an anatomic study and relationship to local anesthesia of the anterior mandibular teeth. J Am Dent Assoc 1984;108:350-2. 20. Berns JM, Sadove MS. Mandibular block injection: a method of study using an injected radiopaque material. J Am Dent Assoc 1962;65:736-45. 21. Galbreath JC, Eklund MK. Tracing the course of the mandibular block injection. Oral Surg Oral Med Oral Pathol 1970;30:571-82. 22. Fiset L, Getz T, Milgrom P, Weinstein P. Local anesthetic failure: diagnosis and management strategies. General Dentistry 1989;5:414-7. 23. Weil C, Santangelo C, Welham FS, Yackel RF. Clinical evaluation of mepivacaine HCL by a new method. J Am Dent Assoc 1961;63:26-32. 24. Replogle K, Reader A, Nist R, Beck M, Weaver J, Meyers W. Cardiovascular effects of the intraosseous injection of 2% lidocaine with 1:100,000 epinephrine and 3% mepivacaine. J Am Dent Assoc. In press 1999.

25. Tainter ML, Throndson AH. Influence of vasoconstrictors on the toxicity of procaine anesthetic solutions. J Am Dent Assoc 1938;25:966-79. 26. Luduena FP, Hoppe JO, Oyen IH, Weissinger GD. Some pharmacologic properties of levo- and dextro-nordefrin. J Dent Res 1958;37:206-13. 27. Robertson VJ, Taylor SE, Gage TW. Quantitative and qualitative analysis of the pressor effects of levonordefrin. J Cardiovasc Pharmacol 1984;6:929-35. 28. Yagiela J, Duffin S, Hunt L. Drug interactions and vasoconstrictors used in local anesthetic solutions. Oral Surg Oral Med Oral Pathol 1985;59:565-71. 29. Dreyer AC, Offermeier J. The influence of desipramine on the blood pressure elevation and heart rate stimulation by levonordefrin and felypressin alone and in the presence of local anesthetics. Journal of the Dental Association of South Africa 1986;41:615-8.

Reprint requests: Al Reader, DDS, MS Graduate Endodontics College of Dentistry The Ohio State University 305 W. 12th Avenue Columbus, OH 43210

Abstract Wound healing around endosseous implants in experimental diabetes Marc L. Nevins, Nadeem Y. Karimbux, Hans Peter Weber, William V. Giannobile, Joseph P. Fiorellini International Journal of Oral and Maxillofacial Implants 1998;13:620-9 Introduction. Diminished wound healing has been reported in patients with diabetes mellitus. Authors have previously suggested that osseointegration of dental implants may be decreased in the diabetic patient. To experimentally evaluate this, diabetes was induced in rats by injection of streptozotocin, and osseointegration was evaluated. Material and Methods. Streptozotocin was delivered by intraperitoneal injection of 40-day-old rats. Blood glucose levels were monitored to assure development of diabetic state in the experimental animals. Custom-fabricated, commercially pure titanium plasma–sprayed cylindrical implants were placed in the femur of the rat. Ten experimental and 10 control rats underwent implant placement. Half of the rats were killed at 4 weeks, and the remaining 10 rats were then killed at 8 weeks after implant placement. Nondecalcified longitudinal sections were obtained. Histomorphometric analysis, including marrow bone density, percentage bone implant contact, and percentage marrow bone-implant contact, was performed. Results. Diabetes was predictably induced in both control and experimental animals. Because of processing difficulties, only 51 of the 60 implants in 19 of the 20 animals were available for evaluation. Osseointegration was found to occur consistently in both the diabetic and control specimens, and the rate of new bone formation in a 250 micrometer zone around the implants was similar for both diabetic and control animals. However, at both 4 weeks and 8 weeks, less bone-implant contact was observed (P < .0001). This study demonstrated that the process of osseointegration is effected by streptozotocin-induced diabetes in the rat. Clinical Significance. While there was a decreased bone-to-implant contact in diabetic rats, it must be recognized that this was in an uncontrolled diabetic state. Clinically, this may imply that patients with uncontrolled diabetes should not receive dental implants. However, the significantly elevated glucose levels produced in the experimental group in this study would not be consistent with what would typically be found in the diabetic patient whose disease is under control. There is nothing in this study to suggest that the controlled diabetic is not a suitable candidate for endosseous implant reconstruction. Peter Larsen The Ohio State University