Injection pain of bupivacaine with epinephrine vs. prilocaine plain
MICHAEL J. WAHL, D.D.S.,
MARGARET M. SCHMITT, D.M.D.,
DONALD A. OVERTON, Ph.D. and
M. KATHLEEN GORDON, Ph.D.
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ABSTRACT
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Background. Prilocaine plain has been described in the literature as causing less pain on injection than bupivacaine with epinephrine, possibly because of the higher pH of the prilocaine anesthetic solution.
Methods. In a double-blind study design, 681 consecutive patients in a general dental practice received maxillary buccal infiltration, posterior palatal infiltration or inferior alveolar block injections, administered under clinical conditions by one of two dentists. Immediately after injection, patients rated the pain from each injection on a six-point scale. The pain response was analyzed according to treating dentist, location of injection, patient’s sex and anesthetic administered.
Results. The reported pain on injection of bupivacaine with epinephrine was significantly greater than that of prilocaine plain. Patients reported no significant difference in pain at different injection locations, except that palatal injections caused significantly more reported pain than did anterior maxillary infiltration, posterior maxillary infiltration or inferior alveolar block injections.
Conclusions. Under clinical conditions, the injection of bupivacaine with epinephrine causes significantly more perceived pain than does the injection of prilocaine plain.
Clinical Implications. Bupivacaine with epinephrine and prilocaine plain have certain advantages and disadvantages that should be considered before choosing an anesthetic for a dental procedure. A disadvantage of bupivacaine with epinephrine is that it produces more perceived pain than does prilocaine plain.
The discovery of local anesthesia more than one century ago has enabled modern dentistry to be performed almost painlessly. However, the delivery of local anesthetic solutions still can be uncomfortable, with pain resulting not only from the needle puncturing the mucosa, but also because of properties of the anesthetic solutions themselves. Local anesthetic solutions with low pH have been thought to cause a burning sensation and thus more pain than anesthetics with more neutral pH.1 As a result, some investigators have asserted that prilocaine plain (4% Citanest Plain, AstraZeneca Pharmaceuticals LP, Wilmington, Del. [marketed by Dentsply Pharmaceuticals, York, Pa.]) (pH, 6.0 to 7.02) elicits less pain on injection than do other anesthetics with lower pH.3,4
The pain of injecting bupivacaine with epinephrine was statistically significantly greater than that of prilocaine plain.
Injected 0.5 percent bupivacaine with epinephrine (Cook-Waite Marcaine, Abbott Laboratories, Abbott Park, Ill. [marketed by Eastman Kodak Co., Rochester, N.Y.]) results in a longer duration of action than does 4 percent prilocaine plain,1 and the choice between these anesthetics often is made after consideration of the expected duration of the procedure. Bupivacaine with epinephrine may be preferred for longer procedures (longer than one hour), while prilocaine plain may be preferred for shorter procedures (less than one hour). In what has been called a "technique for giving painless injections,"3 many dentists inject prilocaine plain first, which they assert painlessly numbs the tissue, before injecting bupivacaine with epinephrine.
Our literature search failed to reveal any studies comparing injection pain of bupivacaine with epinephrine with that of prilocaine plain, but studies have compared pain on injection of other anesthetic solutions with different pH values. Lidocaine with epinephrine has a lower pH (approximately 4.55) than does prilocaine plain (pH, 6.0 to 7.0), so one might expect lidocaine with epinephrine to be more painful than prilocaine plain. The addition of vasoconstrictors to local anesthetic solutions can increase the depth and duration of anesthesia, but also can lower the pH of the anesthetic solution.
In 1999, Kramp and colleagues6 reported that lidocaine with epinephrine caused significantly more pain than did prilocaine plain. Our 2001 study of the same drugs showed a trend in the same direction, although the difference was not statistically significant.7
In a 1994 randomized, placebo-controlled, double-blind study, Howe and Williams8 reported that bupivacaine with 1:200,000 epinephrine caused more intradermal injection pain than did lidocaine with 1:200,000 epinephrine. Buffering of bupivacaine can increase its pH and decrease injection pain compared with unbuffered bupivacaine.8–10
The present study compared 4 percent prilocaine plain with 0.5 percent bupivacaine with 1:200,000 epinephrine. Because the latter drug has a significantly lower pH (3.3 to 5.5) (James E. Flood, product line manager, anesthetics, Eastman Kodak Co., written communication, Oct. 25, 2002) than prilocaine plain (pH, 6.0 to 7.0),2 we hypothesized that there would be a significant difference in injection pain between the two drugs. We performed this study to confirm this expectation, as well as to obtain an estimate of how much more pain was produced by bupivacaine with epinephrine than by prilocaine plain and of how clinically important any difference might be.
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PATIENTS, MATERIALS AND METHODS
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The study sample was composed of 681 consecutively seen patients older than 18 years of age with no medical contraindications who were scheduled for routine dental procedures with one of two general dentists (M.W. [dentist 1] and M.S. [dentist 2]) between Jan. 4, 2000, and Nov. 7, 2000. All patients were asked by the dentist to rate the painfulness of an injection they had just received. In patients who received multiple injections, only the first injection received was rated.
We purchased topical 20 percent benzocaine anesthetic and cartridges of prilocaine 4 percent plain and bupivacaine with 1:200,000 epinephrine from a commercial dental supply company. A research assistant removed the manufacturer’s sticker from each anesthetic cartridge and replaced it with a coded sticker to blind both the dentists and patients to the identity of the anesthetic used.
Administration of anesthetics.
We first applied topical anesthetic with a cotton applicator approximately five to 10 seconds before the injections were administered. For maxillary teeth, buccal infiltration injections were used; for mandibular teeth, inferior alveolar block injections were used. Posterior palatal injections were used only by dentist 1. After aspirating, the dentist injected the anesthetic solution slowly to minimize discomfort. For maxillary injections, the dentist used a short (approximately 1-inch) 25-gauge needle and deposited approximately one-half of a cartridge (0.9 milliliters) of anesthetic solution. For mandibular injections, a long (approximately 1
-inch) 25-gauge needle was used and one cartridge (1.8 mL) of anesthetic solution was deposited.
Immediately after the injection, we asked patients to rate their pain on a six-point scale:
- – 0 = no pain;
- – 1 = mild pain;
- – 2 = moderate pain;
- – 3 = distressing pain;
- – 4 = horrible pain;
- – 5 = unbearable pain.11
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RESULTS
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A total of 681 injections were included in the analysis. Dentist 1 administered 292 maxillary buccal infiltration and inferior alveolar block injections, and dentist 2 administered 299 such injections. Dentist 1 also administered 90 posterior palatal injections. The mean age of the study participants was 47 years, with a range from 18 to 89 years. After maxillary buccal infiltration or inferior alveolar injections of bupivacaine with epinephrine, the number of pain ratings of 0, 1, 2, 3, 4 and 5 were 40, 120, 92, 41, 6 and 1, respectively. After maxillary buccal infiltration or inferior alveolar injections of prilocaine plain, the number of pain ratings of 0, 1, 2, 3, 4 and 5 were 134, 116, 27, 14, 0 and 0, respectively (Table 1
). The overall mean pain scores for bupivacaine and prilocaine were 1.5 and 0.7, respectively, for nonpalatal injections.
We evaluated nonpalatal pain scores using a four-factor analysis of variance, or ANOVA, to evaluate the statistical significance of the effects of the following four independent variables:
- – location: three levels (upper anterior infiltration, upper posterior infiltration, inferior alveolar block);
- – drug: two levels (bupivacaine or prilocaine);
- – dentist: two levels (M.W. or M.S.);
- – sex of patient: two levels (male or female).
The ANOVA showed significant effects of drug (P < .0005) and patient’s sex (P < .005). The effect of dentist also was significant (P = .03), but the effect of injection location was not significant (P = .6). We used student t tests to evaluate the significance of differences between specific groups.
Mean pain scores.
Table 2 shows the mean pain scores after each drug was administered at each of the three nonpalatal injection locations. Student t tests showed that bupivacaine with epinephrine produced a significantly higher pain response than did prilocaine plain at each of the nonpalatal injection sites. Table 3 shows the mean pain scores of male and female patients of the two treating dentists after nonpalatal injections. For each dentist, the mean pain score of female patients was significantly higher than that of male patients.
Three-factor ANOVA.
To contrast the pain scores after posterior palatal injections with those after nonpalatal injections, we performed a three-factor ANOVA on data for the patients of dentist 1 only, comparing posterior palatal scores with nonpalatal scores pooled across all three nonpalatal injection sites. The factors were as follows:
- – location: two levels (all nonpalatal vs. posterior palatal);
- – patient’s sex: two levels (male vs. female);
- – anesthetic: two levels (bupivacaine vs. prilocaine).
This ANOVA yielded a significant effect of anesthetic (P < .0005) and location of injection (P < .0005). The effect of the patient’s sex was nonsignificant (P = .24). Table 4 shows mean pain scores. Student t tests revealed significant differences between pain scores after bupivacaine and prilocaine were administered in both nonpalatal and palatal locations (Table 4).
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DISCUSSION
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The data unambiguously show that injection of bupivacaine with epinephrine produced higher pain response scores than did injection of prilocaine plain, with the difference being statistically significant at each intraoral location tested. The data also suggest that palatal injections produce more pain than do nonpalatal injections. The difference between anesthetics was clinically significant, as the pain scores after administration of bupivacaine with epinephrine were approximately twice those after administration of prilocaine plain at each nonpalatal location.
Palatal injection pain.
Patients rated injections at the posterior palatal location as more painful than those at other sites, probably because of the pressure created by injecting in a region of firmly attached tissue. In addition, patients reported a greater pain response from bupivacaine in palatal locations than that from prilocaine in the same locations.
Injection of bupivacaine with epinephrine produced higher pain response scores than did injection of prilocaine plain.
The two dentists used different procedures to mask the pain of injection. Dentist 1 typically shook the patient’s lip while injecting the anesthetic. Dentist 2 usually asked patients to inspect posters on the ceiling while injecting the anesthetic. Perhaps because of these differing procedures, patients’ pain responses differed significantly between the two dentists.
Female patients reported higher pain scores than did male patients, irrespective of whether the treating dentist was male or female.
Kramp and colleagues6 and we7 reported that the injection pain of lidocaine with epinephrine was slightly greater than the injection pain of prilocaine plain, although in our data, the difference was not statistically significant. This difference in reported pain probably occurred because lidocaine with epinephrine has a lower pH than prilocaine plain.
Bupivacaine vs. prilocaine.
In the present study, the injection pain of bupivacaine with epinephrine was significantly greater than the injection pain of prilocaine plain. The difference between the pH of bupivacaine with epinephrine and prilocaine plain (at most 3.7) is much greater than the difference between the pH values of lidocaine with epinephrine and prilocaine plain (at most about 2.5), and it appears that the difference in pain is related to the difference in pH.
The technique of injecting prilocaine plain relatively painlessly and then bupivacaine with epinephrine should cause less injection pain than the injection of bupivacaine with epinephrine alone. It is possible, however, that the two injections used in this technique could cause more postoperative pain than a single injection. Further investigation is warranted.
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CONCLUSION
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The data show that under the clinical conditions of this study, patients usually reported experiencing only mild or no injection pain when prilocaine plain was administered, and usually reported experiencing moderate, mild or no injection pain when bupivacaine with epinephrine was administered. The pain of injecting bupivacaine with epinephrine was statistically significantly greater than that of prilocaine plain. No significant difference existed in perceived injection pain between maxillary buccal anterior infiltration, maxillary buccal posterior infiltration and inferior alveolar block injections. Patients reported that posterior palatal injections were more painful than maxillary buccal anterior infiltration, maxillary buccal posterior infiltration and inferior alveolar block injections. The painfulness of local anesthetic injections may be related to the pH of the injected solution.
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Dr. Wahl is in private practice, Wahl Family Dentistry, 1601 Concord Pike, Wilmington, Del. 19803, e-mail "WahlMichaelJ{at}aol.com". Address reprint requests to Dr. Wahl.
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FOOTNOTES
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Dr. Overton is a professor, Department of Psychology, Temple University, Philadelphia.
Dr. Gordon is an adjunct associate professor, University of Delaware, Newark.
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REFERENCES
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- Malamed SF. Handbook of local anesthesia. 4th ed. St. Louis: Mosby; 1997.
- 4% Citanest Plain [package insert]. Wilmington, Del.: AstraZeneca LP; 2000.
- Strupp W. A clinical technique for giving painless injections. Dent Today 1998;17(12):34–7.[Medline]
- Jones D. Smooth running in a small office. Dent Today 1999;18(4):8–10.
- Physicians’ desk reference: PDR, 1995. 49th ed. Montvale, N.J.: Medical Economics Data Production; 1995:580.
- Kramp LF, Eleazer PD, Scheetz JP. Evaluation of prilocaine for the reduction of pain associated with transmucosal anesthetic administration. Anesth Prog 1999;46(2):52–5.[Medline]
- Wahl MJ, Overton D, Howell J, Siegel E, Schmitt MM, Muldoon M. Pain on injection of prilocaine plain vs. lidocaine with epinephrine: a prospective double-blind study. JADA 2001;132:1396–401.
- Howe NR, Williams JM. Pain of injection and duration of anesthesia for intradermal infiltration of lidocaine, bupivacaine, and etidocaine. J Dermatol Surg Oncol 1994;20:459–64.[Medline]
- Jones JS, Plzak C, Wynn BN, Martin S. Effect of temperature and pH adjustment of bupivacaine for intradermal anesthesia. Am J Emerg Med 1998;16(2):117–20.[Medline]
- Cheney PR, Molzen G, Tandberg D. The effect of pH buffering on reducing the pain associated with subcutaneous infiltration of bupivacaine. Am J Emerg Med 1991;9(2):147–8.[Medline]
- Hutchins HS Jr, Young FA, Lackland DT, Fishburne CP. The effectiveness of topical anesthesia and vibration in alleviating the pain of oral injections. Anesth Prog 1997;44:87–9.[Medline]
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ABSTRACT
PATIENTS, MATERIALS AND METHODS
