Evaluation of New Gingival Retraction Agents W.H. BOWLES, S.J. TARDY, and A. VAHADI Department of Biochemistry, Baylor College of Dentistry, 3302 Gaston Avenue, Dallas, Texas 75246 Current gingival retraction agents are not without undesirable side-effects; there appears to be no ideal gingival retraction agent. Several sympathomimetic amines, capable of producing local vasoconstriction with minimal systemic side-effects, are available as non-prescription nasal decongestants and eye washes. The purpose ofthis study was to evaluate the efficacy of three ofthese agents for gingival tissue displacement. Mongrel dogs were used as experimental subjects, in which pulse rate and blood pressure were monitored electronically. Visine® (tetrahydrozoline HCl, 0.05%), Afrin® (oxymetazoline, 0. 05%), and Neosynephrine® (phenylephrine HCl, 0.25%) were the commercial products studied as gingival retraction agents. Plain, untreated cord was used as a mechanical control, and as a vehicle for the three experimental agents. Commercially available cords impregnated with both racemic epinephrine (8%) and alum were also used as standard retraction agents with which the test solutions were compared. Visine and Afrin produced tissue displacement greater than that of any of the other agents; Neosynephrine, epinephrine, and alum were more effective than the untreated mechanical control. Cardiovascular changes included a slight increase in systolic pressure in the Neosynephrine group, and a slightly lower mean arterial pressure and pulse rate in all three experimental groups. J Dent Res 70(11):1447-1449, November, 1991

Introduction. Advertising by dentists, coupled with public service announcements sponsored by various dental organizations, have led to a greater public awareness of the value and availability of cosmetic dentistry and, hence, a greater demand for these services. Preparation of teeth for these restorations frequently includes the identification of a subgingival margin or finish line. In order for a satisfactory impression to be obtained, tissue displacement or gingival retraction is necessary. According to Benson et al. (1986), gingival retraction measures fall into one of four major categories: (1) simple mechanical methods, (2) chemo-mechanical methods, (3) rotary gingival curettage, and (4) electro-surgical methods. Of these four categories, the chemo-mechanical method of gingival retraction is the most widely used, as was found in a survey by Donovan et al. (1985). The mechanical aspect ofthis method involves placement of a string into the gingival sulcus to displace the tissues physically. The chemical aspect of the method involves treatment of the string with one or more of a number of compounds that will induce temporary shrinkage ofthe tissues and should also control the hemorrhage and fluid seepage that often accompany subgingival margin preparation. Substances most often used are: racemic epinephrine, 0.1% solution or 8% impregnated cord; alum; aluminum chloride, 5% or 25%; ferric sulfate, 13.3%; or zinc chloride, 8% or 40%. Aluminum chloride and zinc chloride are caustic to gingival tissues and thus are not recommended. Ferric sulfate acts as a clotting agent, and often, when the string is removed, the clot is pulled out with it, and hemorrhage begins anew. Also, ferric sulfate does not cause actual Received for publication August 13, 1990 Accepted for publication June 26, 1991 This investigation was supported in part by Baylor College of Dentistry Student Pre-doctoral Fellowships #SP-887 and #S-8913.

shrinkage of the tissues. Alum acts mainly as an astringent and is considered to be safe and moderately effective as a tissue-displacing agent. Dental supply catalogs are extremely vague about the concentration of chemical agents, frequently failing even to specify the active ingredient. Epinephrine, either supplied as a separate solution or incorporated into the string, has been widely used. In many patients, however, epinephrine produces a syndrome of undesirable sideeffects (Donovan et al., 1985; Benson et al., 1986) that may include tachycardia, increased respiratory rate, hypertension, nervousness, feelings of weakness in the extremities, frank apprehension, and post-operative depression. General anesthesia is sometimes used for full-mouth reconstruction and other extended dental procedures. General anesthetics of the fluorinated-hydrocarbon type, such as halothane, sensitize the myocardium to epinephrine and may produce life-threatening reactions (Price and Dripps, 1965). Thus, care should be taken that epinephrine-containing retraction cord not be used for restorative procedures when halothane or other fluorinated-hydrocarbon general anesthetics are used. Chemical agents used in gingival retraction have recently been reviewed by Nemetz and Seibly (1990). There appears to be no ideal agent for gingival retraction, and therefore, it is considered worthwhile for new agents for this purpose to be explored. There are several vaso-active substances which, when used topically, have relatively few side-effects. These substances are the active ingredients in various over-the-counter (non-prescription) nasal or ophthalmic decongestants: tetrahydrozoline HCl, 0.05% (Visine®); oxymetazoline HCl, 0.05% (Afring); and phenylephrine HCl, 0.25% (Neosynephrine®). They are all classified as sympathomimetic amines and act as alpha-agonists. Local vasoconstrictor actions are most prominent, with minimal systemic effects (Cutting, 1969). Apparently, none ofthese agents has been previously examined as a potential gingival retraction agent. The present studies were undertaken to examine the effectiveness and safety of these three compounds (tetrahydrozoline, oxymetazoline, and phenylephrine) as gingival retraction agents, and to compare their effects with those ofcords impregnated with epinephrine and with alum. Preliminary reports have appeared in abstract form (Tardy and Bowles, 1989; Vahadi and Bowles, 1990).

Materials and methods. Commercially available solutions of the three test agents were used in the form of Visine® (tetrahydrozoline hydrochloride, 0.05%), Afrin® (oxymetazoline hydrochloride, 0.05%), and Neosynephrine®(phenylephrine hydrochloride, 0.25%). These three agents, incorporated into commercially available untreated cord (Retrax®, Pascal), were compared with commercially prepared cords containing 8% racemic epinephrine (Racord®, Pascal), and with alum (Pascord®, Pascal). Untreated cord was used as a mechanical control. Mongrel dogs were used as experimental subjects, with from two to five teeth per quadrant available, depending on the condition of the gingiva. Non-terminal use of dogs in this study was approved by the Animal Care Committee of the Baylor College of Dentistry. Each dog was anesthetized with sodium pentobarbital, 30 mg/kg, i.v. A pediatric or neo-natal blood pressure cuff placed around one ofthe dog's hind legs, with leads attached to a DynaMap® electronic monitor, was found to be suitable for monitoring both pulse rate and blood pressure. This eliminated the need for arterial cannulation, 1447

1448

BOWLES et al.

thus reducing trauma to the dog. Each tooth to be used was marked at the gingival crest with a small bur in a high-speed handpiece. A preliminary impression was made by use of an Accu-Gel® syringe and tray impression material, with a custom acrylic tray, and the cast was poured with improved laboratory stone. The teeth selected for the study were isolated and the retraction medium placed: commercially available, untreated cord as a mechanical control, or commercially prepared cord impregnated with either epinephrine (8%) or saturated alum, or plain cord pre-saturated with one of the test solutions. All cords used, both plain and treated, were from the same manufacturer; they were all the same size, and all were of the twisted type. For the sake of consistency, the packing of the retraction cord was performed by only one individual. The cords were removed after five min, and a second impression was made. Casts were made and compared with the pre-treatment casts. Sections of the casts were sawed out, and the teeth under investigation were sectioned bucco-lingually at the buccal eminence, followed by quantitative measurement of the width of the retracted sulcus, under a low-power microscope equipped with a 0.25-mm grid. The width was measured as the distance from the tooth to the crest of the gingiva. After ten days, the tissues of the dogs' mouths were reexamined for evidence of recession by comparison ofthe crest of the gingiva with the original mark. The techniques used in this study are standard procedures that have been used to evaluate most of the gingival retraction agents that are currently in clinical use (Woychesin, 1964).

Results. Statistical analysis of the data included analysis of variance, followed by ScheffM's test for multiple comparisons of unequal sample sizes. The depth ofthe gingival sulcus was not significantly affected by any of the test agents. The mean width of the gingival sulcus of each group is shown in Table 1. Analysis of variance showed significant differences among the experimental groups (F ratio = 39.4, p < 0.001). The mean widths (± S.D.) of the retracted sulcus in the Visine® (0.84 ±0.09 mm) andAfrin® (0.80 ±0.09 mm) groups were not significantly different from each other, but were significantly wider than those of all of the other groups (p < 0.001). The width of the retracted sulcus of the Neosynephrineg (0.58 ± 0.09 mm) was significantly greater (p < 0.005) than that of the controls (0.38 ±0.07 mm); the sulcus widths ofthe epinephrine (0.51 ±0.04 mm) and alum (0.49 ±0.02 mm) groups were also significantly greater than that of the control group (p < 0.01), but not significantly different from each other, nor were they significantly different from those of the Neosynephrine® group (p . 0.05). Examination of the dogs' mouths after ten days revealed no permanent gingival depression as a result of treatment with the experimental agents. In this study, because of the difficulty in standardizing the process, no deliberate effort was made to induce gingival bleeding in order to evaluate the abilities of the test agents to control hemorrhage. However, in some cases, a slight amount of hemorrhage was induced by the packing of the cord. It was noted that, in those cases, the test agents all appeared to be quite effective in controlling the seepage. Some differences were noted in the cardiovascular responses of the dogs during application of the various test agents (Table 2). Systolic pressure was elevated by the application of epinephrine, Neosynephrine®, and Afrin®, but only with Neosynephrine® was the difference statistically significant. In the Neosynephrine® and Afrin® groups, the systolic pressure was also significantly higher than in the Visine® group. No significant differences in diastolic pressure were noted among the various groups. The mean arterial pressure was the same in the control and epinephrine groups, while it was actually significantly lower in each of the alpha-agonist groups than in the controls. The mean arterial pressure was also

J Dent Res November 1991

TABLE 1 COMPARISON OF THE EFFECTS OF VARIOUS GINGIVAL RETRACTION AGENTS ON SULCUS WIDTH

Group

n

Control

6

0.38

± 0.07

Alum

8

0.49

± 0.02a

Epinephrine

5

0.51

± 0.04a

Neosynephrine

6

0.58

±

Afrin

6

0.80

± 0.09c

Mean Width (mm) ± S.D.

0.09b

Visine 6 0.84 ± 0.09d Significantly differentfrom: acontrols(p < 0.01); bcontrols(p < 0.005); call other groups except Visine (p < 0.001); and dall other groups except Afrin (p < 0.001).

significantly lower in the Visine® and Afrin® groups than in the epinephrine group. The pulse rate of the epinephrine group was elevated significantly above that of controls, while that of the Neosynephrine® and Afrin® groups was significantly lower. All three alpha-agonist groups had a pulse rate significantly lower than that in the epinephrine group.

Discussion. The use of the DynaMap electronic monitor provided a convenient means for non-invasive monitoring of the cardiovascular responses in the dogs during treatment. Many clinicians appear to be concerned about possible sideeffects from the epinephrine-impregnated retraction cord. Alternative agents include solutions ofzinc, aluminum, or iron salts, which are often caustic to the gingiva. This study suggests that a number of sympathomimetic amines, currently available as non-prescription items for other local applications, may provide safer and more effective alternatives to those agents currently in use. Visine® and Afrin® have similar active ingredients (imidazole derivatives) and appear to be similarly more effective than epinephrine or Neosynephrine® (a phenylethylamine derivative, similar to epinephrine). A gingival retraction agent should be (1) effective for its intended use, (2) safe-both locally and systemically, and (3) the effects should be spontaneously reversible, wearing off in a short time, leaving no permanent tissue displacement. The three agents tested appear to meet these criteria when used in the appropriate quantities. Scarcely any drug is completely free of side-effects, and package inserts accompanying these products list a number of possible side-effects that may occur if used repeatedly, over an extended period oftime. It should be noted, however, that use of any of these agents as a gingival retractant requires only the use of an amount equal to one application as an eye wash or as a nasal decongestant (two drops), and is not repeated at frequent intervals, as one might do with an eye wash or nasal decongestant. Thus, there is little or no chance of an overdose in this application. The possibility of an allergic reaction exists for patients who may be sensitized to the product. As is prudent with any type of medication, careful questioning of the patient as to prior use and any untoward reactions should minimize the risk of such an event. A preliminary clinical trial with a small number of patients has been reported by Tardy et al. (1990), in which Visine® was compared with epinephrine as a gingival retractant. In that study, Visine® was shown to produce approximately 50% greater tissue displacement and

NEW GINGJVAL RETRACTION AGENTS

Vol. 70 No. 11

1449

TABLE 2

COMPARISON OF CARDIOVASCULAR EFFECTS OF EPINEPHRINE AND NEW POTENTIAL GINGIVAL RETRACTION AGENTS MEAN SD

Group (n) Systolic Pressure 104.2 ± 6.5

Diastolic Pressure 48.0 ± 6.0

Mean Arterial Pulse Pressure 75.6 ± 1.5

Pulse Rate 99.4 ± 2.6

Alum (8)

103.4 ± 5.7

48.3 ± 5.2

75.6 ± 2.7

100.3 ± 2.7

Epinephrine (5)

107.6 ± 6.6

48.6 ± 4.5

75.4 ± 3.9

*107.6 ± 2.3

Visine (5)

104.8 ± 3.2

41.8 ± 6.1

*"57.6 ± 3.4

"96.0 ± 1.7

'*125.3 ± 6.9

40.0 ± 4.7

'*66.3 ± 6.0

*"92.9 ± 3.3

Afrin (5) '111.8 ± 3.1 45.2 ± 10.0 * Significantly different from controls (p < 0.001). Significantly different from epinephrine (p < 0.001). Significantly different from Visine (p < 0.001).

*"61.2 ± 2.6

*"92.8 ± 0.98

Control (5)

Neosynephrine (7)

slightly better control ofcrevicular seepage, with no detectable sideeffects. The results of this study and of the preliminary human study show superior tissue displacement compared with that of gingival retractants in current clinical use, and, therefore, these agents warrant a full clinical trial. REFERENCES

BENSON, B.W.; BOMBERG, T.J.; HATCH, R.A.; and HOFFMAN, W. (1986): Tissue Displacement Methods in Fixed Prosthodontics, JProsthet Dent 55:175-181. CUTTING, W.C. (1969): Cutting's Handbook of Pharmacology, 4th ed., New York: Appleton-Century-Crofts, p. 507. DONOVAN, T.E.; GANDARA, B.K.; and NEMETZ, H. (1985): Review and Survey of Medicaments Used with Gingival Retraction Cords, JProsthet Dent 53:525-531. NEMETZ, E.H. and SEIBLY, W. (1990): The Use of Chemical Agents in Gingival Retraction, Gen Dent 38:104-108. PRICE, H.L. and DRIPPS, R.D. (1965): GeneralAnesthetics (continued). II.

Volatile Anesthetics: Diethyl Ether, Divinyl Ether, Chloroform, Halothane, Methoxyflurane, and other Halogenated Volatile Anesthetics. In: The Pharmacological Basis of Therapeutics, 3rd ed., L.S. Goodman and A. Gilman, Eds., New York: The Macmillan Company, p. 93. TARDY, S.J. and BOWLES, W.H. (1989): Evaluation of New Gingival Retraction Agents, JDent Res 68:414, Abst. No. 1861. TARDY, S.J.; BOWLES, W.H.; and CHAMBLESS, L.A. (1990): Preliminary Clinical Evaluation of Visine® (tetrahydrozoline) as a Gingival Retraction Agent, J Prosthet Dent 69:250, Abst. No. 1134. VAHADI, A. and BOWLES, W.H. (1990): Comparison of New Gingival Retraction Agents with Alum-impregnated Cord, J Dent Res 69:250, Abst. No. 1129. WEINER, N. (1985): Norepinephrine, Epinephrine, and the Sympathomimetic Amines. In: The Pharmacological Basis of Therapeutics, 7th ed., L.S. Goodman and A. Gilman, Eds., New York: The Macmillan Company, p. 158. WOYCHESHIN, F.F. (1964): An Evaluation ofthe Drugs Used for Gingival Retraction, J Prosthet Dent 14:769-776.

Evaluation of new gingival retraction agents.

Current gingival retraction agents are not without undesirable side-effects; there appears to be no ideal gingival retraction agent. Several sympathom...
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