A n ew e x p e rim e n ta l m e th o d o f c a rie s re m o v a l u s in g a 0 .0 5 % s o lu tio n o f N -m o n o c h lo ro g ly c in e (G K-101) b u ffe re d to a pH o f 11.4 has been in v e s tig a te d fo r s a fe ty and e ffe c tiv e n e s s . T h e s o lu tio n has b ee n re p o rte d to be re la tiv e ly n o n to x ic . R e s u lts o f a d o u b le -b lin d c lin ic a l s tu d y c o m p a rin g th e c o m p o u n d w ith s a lin e s o lu tio n (w h e re th e s o lu tio n s w e re a p p lie d to th e le s io n s u s in g a s p e c ia lly d e s ig n e d p u m p w ith a h a n d p ie c e and re m o v a b le tip ) in d ic a te th a t G K -101, w h e n used in th is to ta l syste m , is m o re e ffe c tiv e in re m o v in g c a rio u s m a te ria l th a n th e p la c e b o . A d d itio n a l lo n g -te rm la b o ra to ry s tu d ie s and c lin ic a l tria ls are b e in g c o n d u c te d to d e te rm in e th e s a fe ty and e ffic a c y o f G K-101, in c o m p lia n c e w ith re g u la tio n s o f th e F o o d a nd D ru g A d m in is tra tio n .
A prelim inary report on a chem om echanical m eans of removing caries M e lv in G o ld m an , DDS J o se p h H. K ro n m a n , DDS, PhD, B osto n
■ ■■ ■ ■
A study was designed to evaluate the safety and effectiveness o f a m ethod using 0.05% N -m ono chloroglycine (GK-101) solution for the removal o f carious m aterial from the teeth o f hum ans. Studies with anim als to evaluate the toxicity of the GK-101 solution had been conducted before the initiation o f the clinical trials reported here. T he solution was found to be relatively nontoxic. R esults of tests also had indicated that GK-101 was capable of rem oving carious material from extracted te e th .1 On issuance of an Investigational N ew Drug Perm it (no. 8765) from the F ood and D rug A d m inistration, a clinical study was designed to assess the safety and efficacy of a 0.05% solution of N -m onochloroglycine buffered to a pH of 11.0 to 11.4 for the removal of dental caries. All as pects of this study, including design, control, coding for double-blind sam ples, monitoring, tabulating, and reporting were established and conducted in accordance with the Food and D rug A dm inistration guidelines. Since the m ethod of caries rem oval depends on a chemical substance (GK-101), a delivery system (pum p, handpiece, tip, and so forth), and an operative technique, it was necessary to eval uate the m ethod’s effectiveness in two ways: — A double-blind study for which the hydraulic
and operative elem ents w ere controlled and the action of GK-101 was com pared with that of a placebo (saline) solution for the rem oval of car ies. T he objectives o f this portion of the study w ere twofold: first, to com pare the caries-removing efficacy and safety o f GK-101 against a placebo solution; and, second, to evaluate the effects or side effects of the chemical. — An open study using only the test solution (GK-101) in which the m echanical and operative elem ents w ere evaluated. To establish the design for the double-blind study, it was necessary to establish a suitable control with which the test solution could be com pared. Some questions were posed about the com parison of saline solution at an alm ost neutral pH and the GK-101 solution at a pH above 11.0. A laboratory study on extracted teeth was conducted1 in which the caries-rem ov ing efficacy of GK-101 was com pared with that of normal saline solution and with that of a buffer solution at pH 11.1 Although GK-101 was sta tistically superior to the saline and buffer solu tions (PcO.OOl), no statistically significant dif ference was noted betw een the buffer and saline solutions. Saline solution, therefore, was deem ed a suitable control for the proposed double-blind study. JADA, Vol. 93, D ecem ber 1976 ■ 1149
Methods and materials
GK-101 (0.05% N-monochloroglycine) solution contains 0.05 M glycine, 0.05 M N aO H , 0.05 M NaCl, and 0.05% NaOCl. The solution, which should be used immediately, is prepared by mix ing equal parts of solutions A and B. Solution A consists of 25 ml 2 M NaCl, 25 ml 2 M N aO H , and 25 ml 2 M glycine; (make up to 500 ml with distilled water). F or solution B, 10 ml of 4% to 6 % NaOCl is added to 490 ml distilled water im mediately before mixing with solution A. To deliver the solution to the caries, a special delivery system was devised that included a pump, handpiece, and tip. It was found that a pulsed stream, at 650 pulses per minute, seemed to most effectively remove caries. The stream velocity at the tip was set to deliver 45 to 55 ml/ minute to minimize splashing. This seemed to be an acceptable rate and was comfortable for the patient. The solution was freshly mixed, placed in the reservoir of the pump, and warmed to 105 F. The temperature of the solution was approximately 98 F as it came out of the tip. The handpiece of the pump was similar in size and shape to the conventional straight handpiece and was fitted with a disposable, 2 0 -mm long, lock ing needlelike tip, equivalent in size to a 2 0 -gauge needle. It had a 45° bend to permit easy access to all parts of the cavity. The technique of use involved a paintbrush like motion with the tip touching the carious den tin with very light pressure. This can be more easily learned if the patient does not have anes thesia. The amount of pressure can be gauged quite well, because excessive pressure would cause the patient pain. If heavy pressure were used, the tip’s sharp point would dig into soft caries and the egress of the solution would be blocked. During application of the solution, some of the gross caries was lifted and loosened by the tip and carried away by high-volume evac uatore. It was often desirable to use a spoon ex cavator to remove carious material in undercut areas not readily accessible to the solution.
Double-blind study
The test and the placebo solutions were pack aged identically and labeled with only the sub ject and study numbers. The investigator, there fore, was unable to identify the test or the place bo solution. Arrangements were made for a 1150 ■ JADA, Vol. 93, December 1976
sealed code, which could be made available if a subject experienced untoward side effects. This enabled the investigator to allow for treat ment of such a patient if the need arose. After the study was completed, all unused supplies, all sealed coded envelopes, all case reports, evalua tions, and other material related to the study were returned to the outside laboratory that had prepared the material. The code was then brok en, and the accumulated data were statistically analyzed. Forty men, ages 21 to 50, were selected to par ticipate in the study. Each received a baseline examination with a mouth mirror and explorer to check for caries. Soft tissues also were exam ined to determine if clinical pathosis was evi dent; all subjects in this study were free of any apparent soft tissue pathosis. In addition to the clinical examination, a periapical radiograph was taken of each tooth to be used; only those teeth shown on the radiograph to be normal were used. A complete medical history for each participant was obtained; no one with a history of system ic disease or current drug use was chosen. The tooth to be used in the study had to be vital, with a favorable response to the pulp test er, as well as to percussion and palpation. Only teeth with buccal or labial Class V lesions were selected because these lesions are readily avail able to close, direct inspection. Suspected cases of carious exposure were not included. No other restrictions as to the severity of the caries were considered. One of the 40 subjects was eliminat ed from the study because the lesion size was too small. Patients were scheduled for treat ment within two weeks of the aforementioned screening procedures. Each subject was informed that the solution, as far as is known, is not toxic and that no harm was anticipated if small amounts were swal lowed. The materials were supplied in kits so that 1 liter of solution was available for use on each subject. If no appreciable effect was observed after approximately half a liter was used, the unknown solution was recorded as being inef fective, and the use of that solution was discon tinued. The extent of removal of the carious ma terial was clinically evaluated by the investiga tor on a numerical scale that ranged from 0 (no reaction) to 4 (total removal of the caries). Local anesthetic was not used in any case. Cavity prep aration was not completed at this time, but ade quate access was obtained by conventional means. In the event that no removal of caries was noted, or if only partial removal had been ef
fected, conventional procedures were then used to remove the remaining carious material. Then the cavity was irrigated, dried, and temporarily filled with zinc-oxide and eugenol. Of the 39 sub jects in the study, 38 returned one month after treatm ent and the final restoration was placed. Conventional rotary instrumentation was used, as required, to complete the cavity preparation, before placement of the restorative material. Blood and urine samples of all patients were collected 15 minutes before treatm ent, two hours after treatm ent, and one month after treatment. The laboratory tests for the blood included a test for hemoglobin, a hematocrit, white blood cell count, as well as a differential count. The urine was tested for specific gravity, sugar, albumin, pH , and sediment. At the one month recall, an intraoral examination was performed for each patient; the soft tissue examination, pulp test ing, periapical radiograph, and all laboratory tests previously described were also repeated. Subjective symptoms were also evaluated. Comments by the patients were included in the report obtained for each patient. All data ob tained were recorded individually for each sub ject. Any adverse reactions were to be noted and reported immediately to the monitor. (The monitor is a requirement of the FD A . This per son observes the study and makes certain that all procedures are performed according to the proto col. The monitor, however, does not participate in the study.) A written report of any adverse effect was to be submitted immediately by the investigator. No adverse effects were observed. ■ Findings: Statistical evaluation indicated that the patient groups were comparable in terms of age distribution. Results of pretreatment and posttreatment intraoral examinations were also comparable. The amount of solution used ranged from 170 to 800 cc for the GK-101 and from 175 to 600 cc for the placebo. Of the 38 patients who completed the double blind portion of the study, 19 received treatment using the test solution. Caries removal was re corded as total in 15 (80%); caries was almost completely removed in one (5%); in two (10%) caries was partially removed; and in one (5%) surface removal only was recorded. Difficult access was recorded for the lesions in the latter three subjects; this may explain the poor ratings received by them (15%). For the 19 subjects in the placebo group, caries removal was recorded as total for two ( 1 0 %) and as almost total for six
(32%); partial removal was recorded for eight (42%); and surface removal only was recorded for three (16%). The statistical analysis (chi square) indicated that GK-101 was significantly superior to the placebo in the removal of caries (P C 0 .0 1 ).
Because the pump was not self-primed, pos sibly there was a mixing effect from the resid uals of solutions applied earlier. This could have diluted both the test and placebo solutions. The net effect of this dilution may have reduced the efficacy of the test solution and increased that of the placebo. The pump has been redesigned to eliminate this action. The pump appeared to have a hydraulic effect on the removal of soft debris, and the tip me chanically lifted and removed small portions of carious material that had been softened by the solution. Therefore, it was concluded that the results obtained in caries removal were the result of the chemical action of the GK-101 plus the mechanical and hydraulic effects of the needle like tip and the stream of liquid. N o statistically significant differences were computed in hemoglobin, hematocrit, or white blood cell counts when test results for subjects receiving the placebo solution or GK-101 solu tion were compared. A statistically significant reduction in lymphocytes was observed two hours after treatment in some patients receiving the test solution. A similar reduction of lymph ocytes also was observed in the placebo group. The reductions in lymphocytes were so similar that, when the groups were compared, there were no statistically significant differences be tween the groups receiving the test and placebo solutions. The lymphocyte level in the subjects in both groups had returned to the pretreatment levels by the one-month recall. Eight patients in the placebo group showed a transition from the normal range to a higher or lower lymphocyte range; only five such transitions were noted in those patients receiving GK-101.
O pen study
The second study was an open study. The solu tion used was known to be GK-101 and the pur pose was to evaluate the technique of use. Fifty male patients, of comparable age to those in the first part of the study, were selected. The same criteria of tooth selection applied, except that all classifications of cavities (Classes I, II, III, IV ,
Goldman—Kronm an: CHEMOMECHANICAL MEANS OF CARIES REMOVAL ■ 1151
Table ■ Ratings for caries removal in 61 carious teeth treated with GK-101, in con junction with the pump system. No. lesions treated
Class
Total removal
Alm ost total to total removal
Partial removal
Other ratings
1
2
2
0
0
II III IV V
24 18
24 17
0
0
0
0
1
0 0
Total
0
1
1
0
0
16 61
14 58
2
0
0
2
1
0
Note: For testing the hypothesis that GK-101 solution is 100% effective in “ total” removal: t =(1.951/V(0.951)(0.049)/61 = 1.78. The critical value of this is 1.96). Patient no. 37 refused to participate in the treatm ent and w as not included in this table.
and V) were accepted. Sixty-one teeth in 49 pa tients were used because one patient refused treatment; therefore, the results are based on the treatm ent of 49 patients. Some of the lesions were small, some were of average size, but many were deep and exten sive. In these latter lesions, a spoon excavator was used to remove gross, superficial caries, which seemed to soften after two or three min utes of exposure to GK-101. This was done only to speed up the process, removing the outer mass of debris-mixed caries to get to the more typical caries to be used in testing the solution and evaluating the technique. ■ Findings: On the basis of caries removal re sults (Table), GK-101 solution, in conjunction with the pump system, was found to be effective in total removal of caries. As shown in the Table, the caries in all but one of the 61 teeth treated with GK-101 was rated as “ total removal” (58) or as “ almost total to total” removal (2). Since this open study was done for the purpose of eval uating technique, much of the caries that was re moved by a spoon was removed in that manner to hasten the process, rather than because the solution would not remove the caries. The amount of solution used ranged from 200 cc to 1,300 cc. One Class II cavity required 1,300 cc; this tooth was a completely broken-down molar and when the caries removal was com plete, practically no crown remained. For 77% of the lesions treated, the patients were free of pain, and no unpleasant taste or discomfort was reported. However, if pain was reported, in all instances, it was designated by the patients as “ slight” or “ little” in nature. No side effects were reported by patients during the course of the study. In one patient the solution did not remove the caries, which was a very hard, black type that could not even be removed by a spoon excava tor, and so a bur was used. 1152 ■ JADA, Vol. 93, December 1976
Discussion
D irect access is absolutely essential to the caries removal efficacy of GK-101. If the access was not good, and if the caries was not well exposed, the solution did not remove the carious mater ial as readily. If there was good access, the car ies was removed relatively rapidly and painless ly. The solution was suctioned away by high speed evacuation. It should be emphasized at this point that the use of the solution did not eliminate all need for instrumentation in the preparation of the cavity. It was necessary in some cases to establish good access with a ro tary instrument. In such cases, the patient was informed, and instrumentation was undertaken. After the caries had been removed, it was nec essary to create retention form for the filling with a rotary instrument. Small amounts of caries that were not readily accessible sometimes remained after use of the GK-101 solution and these had to be removed before the tooth was filled. Removal was achieved by a spoon excavator or by a bur. Unsupported enamel was removed by the use of chisels or other conventional instrumentation. Various kinds of caries seemed to react differ ently to the solution. F or instance, soft, rubbery caries seemed to be the most rapidly and most easily removed by GK-101. The leathery, darkstained decay of root caries, or the dark, arrested caries that had been present on a tooth for long periods of time were the most difficult to re move. They were removed by the solution, how ever, but more slowly. Sometimes, after all car ies had been removed as indicated by checking with hand instruments, small areas of stain still remained in the cavity. The solution would not remove this stain and its removal (by conven tional means) was optional at the discretion of the operator. All classifications of cavities were treated, Classes I, II, III, IV , and V. In large cavities
with large amounts of caries, after the solution was applied for two to three minutes, the caries seemed to be considerably softened and light pressure with a sharp spoon excavator could remove substantial portions of it without pain. Application of GK-101 was then continued until all the caries accessible to the spray had been removed. Several of the teeth used in the study had frank pulp exposures but unless the expo sure was touched with the tip, there was no pain from the spraying of the solution. Deep cavities, in which it was suspected that there would be pulp exposures, as well as moderate and shallow cavities, were included in the study. The mean time required for caries removal with the GK-101 pump system was approxim ately 8 Vi minutes. The time involved to prepare the cavity to receive a temporary filling was con sistent with the time usually required with con ventional methods (including the time neces sary for anesthesia). An important factor was that the action of the solution appeared to be selective; that is, it re moved only carious dentin and did not affect, as far as could be determined, the sound den tin. In contrast to a rotary cutting instrument, the effects of heat and pressure on the pulp also were eliminated. Of course, the operator had to determine when the cavity had been fully cleansed of all caries and when further steps had to be taken either to remove any remaining bits of caries or to prepare the retention form with a bur for proper filling. In this two-part study, 87 patients with 99 car ious teeth were treated. From these studies, we conclude that: —GK-101 does have a chemical action in car ies removal; the method is currently under inves tigation. —The pump and the mechanism that is used to direct the stream o f liquid on the tooth’s surface has specific mechanical action. The removal of caries seems to be partly mechanical, partly chemical, and partly hydraulic. Together the three effectively remove caries. One without the others is not as effective as is the combination. —Patient acceptance was excellent in almost
every instance. When pain was experienced, it was described as “ slight” or “ little.”
Sum m ary
Extensive testing for the safety of the GK-101 solution was conducted with experimental ani mals. An Investigational N ew Drug permit was awarded by the Food and Drug Administration before clinical studies. Subsequently, two stud ies—one double-blind and one open—were con ducted to determine the safety and caries-re moving efficacy of a 0.05% solution of N-monochloroglycine (GK-101) on clinical subjects, as well as to study the technique for such a proce dure. In the double-blind study, the efficacy, as shown by ratings for caries removal, of GK-101 applied under pressure was significantly greater than that of the placebo solution of normal sal ine (P
A prelim inary report on a chem om echanical m eans of removing caries M e lv in G o ld m an , DDS J o se p h H. K ro n m a n , DDS, PhD, B osto n
■ ■■ ■ ■
A study was designed to evaluate the safety and effectiveness o f a m ethod using 0.05% N -m ono chloroglycine (GK-101) solution for the removal o f carious m aterial from the teeth o f hum ans. Studies with anim als to evaluate the toxicity of the GK-101 solution had been conducted before the initiation o f the clinical trials reported here. T he solution was found to be relatively nontoxic. R esults of tests also had indicated that GK-101 was capable of rem oving carious material from extracted te e th .1 On issuance of an Investigational N ew Drug Perm it (no. 8765) from the F ood and D rug A d m inistration, a clinical study was designed to assess the safety and efficacy of a 0.05% solution of N -m onochloroglycine buffered to a pH of 11.0 to 11.4 for the removal of dental caries. All as pects of this study, including design, control, coding for double-blind sam ples, monitoring, tabulating, and reporting were established and conducted in accordance with the Food and D rug A dm inistration guidelines. Since the m ethod of caries rem oval depends on a chemical substance (GK-101), a delivery system (pum p, handpiece, tip, and so forth), and an operative technique, it was necessary to eval uate the m ethod’s effectiveness in two ways: — A double-blind study for which the hydraulic
and operative elem ents w ere controlled and the action of GK-101 was com pared with that of a placebo (saline) solution for the rem oval of car ies. T he objectives o f this portion of the study w ere twofold: first, to com pare the caries-removing efficacy and safety o f GK-101 against a placebo solution; and, second, to evaluate the effects or side effects of the chemical. — An open study using only the test solution (GK-101) in which the m echanical and operative elem ents w ere evaluated. To establish the design for the double-blind study, it was necessary to establish a suitable control with which the test solution could be com pared. Some questions were posed about the com parison of saline solution at an alm ost neutral pH and the GK-101 solution at a pH above 11.0. A laboratory study on extracted teeth was conducted1 in which the caries-rem ov ing efficacy of GK-101 was com pared with that of normal saline solution and with that of a buffer solution at pH 11.1 Although GK-101 was sta tistically superior to the saline and buffer solu tions (PcO.OOl), no statistically significant dif ference was noted betw een the buffer and saline solutions. Saline solution, therefore, was deem ed a suitable control for the proposed double-blind study. JADA, Vol. 93, D ecem ber 1976 ■ 1149
Methods and materials
GK-101 (0.05% N-monochloroglycine) solution contains 0.05 M glycine, 0.05 M N aO H , 0.05 M NaCl, and 0.05% NaOCl. The solution, which should be used immediately, is prepared by mix ing equal parts of solutions A and B. Solution A consists of 25 ml 2 M NaCl, 25 ml 2 M N aO H , and 25 ml 2 M glycine; (make up to 500 ml with distilled water). F or solution B, 10 ml of 4% to 6 % NaOCl is added to 490 ml distilled water im mediately before mixing with solution A. To deliver the solution to the caries, a special delivery system was devised that included a pump, handpiece, and tip. It was found that a pulsed stream, at 650 pulses per minute, seemed to most effectively remove caries. The stream velocity at the tip was set to deliver 45 to 55 ml/ minute to minimize splashing. This seemed to be an acceptable rate and was comfortable for the patient. The solution was freshly mixed, placed in the reservoir of the pump, and warmed to 105 F. The temperature of the solution was approximately 98 F as it came out of the tip. The handpiece of the pump was similar in size and shape to the conventional straight handpiece and was fitted with a disposable, 2 0 -mm long, lock ing needlelike tip, equivalent in size to a 2 0 -gauge needle. It had a 45° bend to permit easy access to all parts of the cavity. The technique of use involved a paintbrush like motion with the tip touching the carious den tin with very light pressure. This can be more easily learned if the patient does not have anes thesia. The amount of pressure can be gauged quite well, because excessive pressure would cause the patient pain. If heavy pressure were used, the tip’s sharp point would dig into soft caries and the egress of the solution would be blocked. During application of the solution, some of the gross caries was lifted and loosened by the tip and carried away by high-volume evac uatore. It was often desirable to use a spoon ex cavator to remove carious material in undercut areas not readily accessible to the solution.
Double-blind study
The test and the placebo solutions were pack aged identically and labeled with only the sub ject and study numbers. The investigator, there fore, was unable to identify the test or the place bo solution. Arrangements were made for a 1150 ■ JADA, Vol. 93, December 1976
sealed code, which could be made available if a subject experienced untoward side effects. This enabled the investigator to allow for treat ment of such a patient if the need arose. After the study was completed, all unused supplies, all sealed coded envelopes, all case reports, evalua tions, and other material related to the study were returned to the outside laboratory that had prepared the material. The code was then brok en, and the accumulated data were statistically analyzed. Forty men, ages 21 to 50, were selected to par ticipate in the study. Each received a baseline examination with a mouth mirror and explorer to check for caries. Soft tissues also were exam ined to determine if clinical pathosis was evi dent; all subjects in this study were free of any apparent soft tissue pathosis. In addition to the clinical examination, a periapical radiograph was taken of each tooth to be used; only those teeth shown on the radiograph to be normal were used. A complete medical history for each participant was obtained; no one with a history of system ic disease or current drug use was chosen. The tooth to be used in the study had to be vital, with a favorable response to the pulp test er, as well as to percussion and palpation. Only teeth with buccal or labial Class V lesions were selected because these lesions are readily avail able to close, direct inspection. Suspected cases of carious exposure were not included. No other restrictions as to the severity of the caries were considered. One of the 40 subjects was eliminat ed from the study because the lesion size was too small. Patients were scheduled for treat ment within two weeks of the aforementioned screening procedures. Each subject was informed that the solution, as far as is known, is not toxic and that no harm was anticipated if small amounts were swal lowed. The materials were supplied in kits so that 1 liter of solution was available for use on each subject. If no appreciable effect was observed after approximately half a liter was used, the unknown solution was recorded as being inef fective, and the use of that solution was discon tinued. The extent of removal of the carious ma terial was clinically evaluated by the investiga tor on a numerical scale that ranged from 0 (no reaction) to 4 (total removal of the caries). Local anesthetic was not used in any case. Cavity prep aration was not completed at this time, but ade quate access was obtained by conventional means. In the event that no removal of caries was noted, or if only partial removal had been ef
fected, conventional procedures were then used to remove the remaining carious material. Then the cavity was irrigated, dried, and temporarily filled with zinc-oxide and eugenol. Of the 39 sub jects in the study, 38 returned one month after treatm ent and the final restoration was placed. Conventional rotary instrumentation was used, as required, to complete the cavity preparation, before placement of the restorative material. Blood and urine samples of all patients were collected 15 minutes before treatm ent, two hours after treatm ent, and one month after treatment. The laboratory tests for the blood included a test for hemoglobin, a hematocrit, white blood cell count, as well as a differential count. The urine was tested for specific gravity, sugar, albumin, pH , and sediment. At the one month recall, an intraoral examination was performed for each patient; the soft tissue examination, pulp test ing, periapical radiograph, and all laboratory tests previously described were also repeated. Subjective symptoms were also evaluated. Comments by the patients were included in the report obtained for each patient. All data ob tained were recorded individually for each sub ject. Any adverse reactions were to be noted and reported immediately to the monitor. (The monitor is a requirement of the FD A . This per son observes the study and makes certain that all procedures are performed according to the proto col. The monitor, however, does not participate in the study.) A written report of any adverse effect was to be submitted immediately by the investigator. No adverse effects were observed. ■ Findings: Statistical evaluation indicated that the patient groups were comparable in terms of age distribution. Results of pretreatment and posttreatment intraoral examinations were also comparable. The amount of solution used ranged from 170 to 800 cc for the GK-101 and from 175 to 600 cc for the placebo. Of the 38 patients who completed the double blind portion of the study, 19 received treatment using the test solution. Caries removal was re corded as total in 15 (80%); caries was almost completely removed in one (5%); in two (10%) caries was partially removed; and in one (5%) surface removal only was recorded. Difficult access was recorded for the lesions in the latter three subjects; this may explain the poor ratings received by them (15%). For the 19 subjects in the placebo group, caries removal was recorded as total for two ( 1 0 %) and as almost total for six
(32%); partial removal was recorded for eight (42%); and surface removal only was recorded for three (16%). The statistical analysis (chi square) indicated that GK-101 was significantly superior to the placebo in the removal of caries (P C 0 .0 1 ).
Because the pump was not self-primed, pos sibly there was a mixing effect from the resid uals of solutions applied earlier. This could have diluted both the test and placebo solutions. The net effect of this dilution may have reduced the efficacy of the test solution and increased that of the placebo. The pump has been redesigned to eliminate this action. The pump appeared to have a hydraulic effect on the removal of soft debris, and the tip me chanically lifted and removed small portions of carious material that had been softened by the solution. Therefore, it was concluded that the results obtained in caries removal were the result of the chemical action of the GK-101 plus the mechanical and hydraulic effects of the needle like tip and the stream of liquid. N o statistically significant differences were computed in hemoglobin, hematocrit, or white blood cell counts when test results for subjects receiving the placebo solution or GK-101 solu tion were compared. A statistically significant reduction in lymphocytes was observed two hours after treatment in some patients receiving the test solution. A similar reduction of lymph ocytes also was observed in the placebo group. The reductions in lymphocytes were so similar that, when the groups were compared, there were no statistically significant differences be tween the groups receiving the test and placebo solutions. The lymphocyte level in the subjects in both groups had returned to the pretreatment levels by the one-month recall. Eight patients in the placebo group showed a transition from the normal range to a higher or lower lymphocyte range; only five such transitions were noted in those patients receiving GK-101.
O pen study
The second study was an open study. The solu tion used was known to be GK-101 and the pur pose was to evaluate the technique of use. Fifty male patients, of comparable age to those in the first part of the study, were selected. The same criteria of tooth selection applied, except that all classifications of cavities (Classes I, II, III, IV ,
Goldman—Kronm an: CHEMOMECHANICAL MEANS OF CARIES REMOVAL ■ 1151
Table ■ Ratings for caries removal in 61 carious teeth treated with GK-101, in con junction with the pump system. No. lesions treated
Class
Total removal
Alm ost total to total removal
Partial removal
Other ratings
1
2
2
0
0
II III IV V
24 18
24 17
0
0
0
0
1
0 0
Total
0
1
1
0
0
16 61
14 58
2
0
0
2
1
0
Note: For testing the hypothesis that GK-101 solution is 100% effective in “ total” removal: t =(1.951/V(0.951)(0.049)/61 = 1.78. The critical value of this is 1.96). Patient no. 37 refused to participate in the treatm ent and w as not included in this table.
and V) were accepted. Sixty-one teeth in 49 pa tients were used because one patient refused treatment; therefore, the results are based on the treatm ent of 49 patients. Some of the lesions were small, some were of average size, but many were deep and exten sive. In these latter lesions, a spoon excavator was used to remove gross, superficial caries, which seemed to soften after two or three min utes of exposure to GK-101. This was done only to speed up the process, removing the outer mass of debris-mixed caries to get to the more typical caries to be used in testing the solution and evaluating the technique. ■ Findings: On the basis of caries removal re sults (Table), GK-101 solution, in conjunction with the pump system, was found to be effective in total removal of caries. As shown in the Table, the caries in all but one of the 61 teeth treated with GK-101 was rated as “ total removal” (58) or as “ almost total to total” removal (2). Since this open study was done for the purpose of eval uating technique, much of the caries that was re moved by a spoon was removed in that manner to hasten the process, rather than because the solution would not remove the caries. The amount of solution used ranged from 200 cc to 1,300 cc. One Class II cavity required 1,300 cc; this tooth was a completely broken-down molar and when the caries removal was com plete, practically no crown remained. For 77% of the lesions treated, the patients were free of pain, and no unpleasant taste or discomfort was reported. However, if pain was reported, in all instances, it was designated by the patients as “ slight” or “ little” in nature. No side effects were reported by patients during the course of the study. In one patient the solution did not remove the caries, which was a very hard, black type that could not even be removed by a spoon excava tor, and so a bur was used. 1152 ■ JADA, Vol. 93, December 1976
Discussion
D irect access is absolutely essential to the caries removal efficacy of GK-101. If the access was not good, and if the caries was not well exposed, the solution did not remove the carious mater ial as readily. If there was good access, the car ies was removed relatively rapidly and painless ly. The solution was suctioned away by high speed evacuation. It should be emphasized at this point that the use of the solution did not eliminate all need for instrumentation in the preparation of the cavity. It was necessary in some cases to establish good access with a ro tary instrument. In such cases, the patient was informed, and instrumentation was undertaken. After the caries had been removed, it was nec essary to create retention form for the filling with a rotary instrument. Small amounts of caries that were not readily accessible sometimes remained after use of the GK-101 solution and these had to be removed before the tooth was filled. Removal was achieved by a spoon excavator or by a bur. Unsupported enamel was removed by the use of chisels or other conventional instrumentation. Various kinds of caries seemed to react differ ently to the solution. F or instance, soft, rubbery caries seemed to be the most rapidly and most easily removed by GK-101. The leathery, darkstained decay of root caries, or the dark, arrested caries that had been present on a tooth for long periods of time were the most difficult to re move. They were removed by the solution, how ever, but more slowly. Sometimes, after all car ies had been removed as indicated by checking with hand instruments, small areas of stain still remained in the cavity. The solution would not remove this stain and its removal (by conven tional means) was optional at the discretion of the operator. All classifications of cavities were treated, Classes I, II, III, IV , and V. In large cavities
with large amounts of caries, after the solution was applied for two to three minutes, the caries seemed to be considerably softened and light pressure with a sharp spoon excavator could remove substantial portions of it without pain. Application of GK-101 was then continued until all the caries accessible to the spray had been removed. Several of the teeth used in the study had frank pulp exposures but unless the expo sure was touched with the tip, there was no pain from the spraying of the solution. Deep cavities, in which it was suspected that there would be pulp exposures, as well as moderate and shallow cavities, were included in the study. The mean time required for caries removal with the GK-101 pump system was approxim ately 8 Vi minutes. The time involved to prepare the cavity to receive a temporary filling was con sistent with the time usually required with con ventional methods (including the time neces sary for anesthesia). An important factor was that the action of the solution appeared to be selective; that is, it re moved only carious dentin and did not affect, as far as could be determined, the sound den tin. In contrast to a rotary cutting instrument, the effects of heat and pressure on the pulp also were eliminated. Of course, the operator had to determine when the cavity had been fully cleansed of all caries and when further steps had to be taken either to remove any remaining bits of caries or to prepare the retention form with a bur for proper filling. In this two-part study, 87 patients with 99 car ious teeth were treated. From these studies, we conclude that: —GK-101 does have a chemical action in car ies removal; the method is currently under inves tigation. —The pump and the mechanism that is used to direct the stream o f liquid on the tooth’s surface has specific mechanical action. The removal of caries seems to be partly mechanical, partly chemical, and partly hydraulic. Together the three effectively remove caries. One without the others is not as effective as is the combination. —Patient acceptance was excellent in almost
every instance. When pain was experienced, it was described as “ slight” or “ little.”
Sum m ary
Extensive testing for the safety of the GK-101 solution was conducted with experimental ani mals. An Investigational N ew Drug permit was awarded by the Food and Drug Administration before clinical studies. Subsequently, two stud ies—one double-blind and one open—were con ducted to determine the safety and caries-re moving efficacy of a 0.05% solution of N-monochloroglycine (GK-101) on clinical subjects, as well as to study the technique for such a proce dure. In the double-blind study, the efficacy, as shown by ratings for caries removal, of GK-101 applied under pressure was significantly greater than that of the placebo solution of normal sal ine (P
