Evaluation of intra-alveolar chlorhexidine dressings after removal of impacted mandibular third molars Pete G. Fotos, DDS, PhD, L%L!?,~ Gerard F. Koorbusch, DDS, LVBA,~ Daniel S. Sarasin, DDS,’ and Richard J. Kist, DDS,d Iowa City, Iowa, and Charleston, S.C. UNIVERSITY






CAROLINA Chlorhexidine gluconate (CHX) has been investigated for its possible benefit in the prevention of alveolar osteitis complicating third molar removal. In a double-blind, placebo-controlled clinical study, 70 randomly selected healthy patients were subjected to uncomplicated mandibular third molar removal followed by CHX-gelatin sponge and saline solution-gelatin sponge intra-alveolar dressings. Each patient was followed for 6 days for postoperative discomfort and complications, and scored accordingly. The results demonstrated that patients receiving 0.2% CHX intra-alveolar dressings exhibited a significant reduction in postoperative discomfort and complications when compared with saline solution-treated control sites (p < 0.005). Further, this phenomenon was not found to be related to patient factors including age, sex, and race, nor did any correlation exist between treated or control sites, and surgical factors including performing surgeon, surgeon’s dominant hand, time of surgery, surgical site, and difficulty of the removal. These findingIs warrant further studies concerning the apparent clinical benefit of postextraction intra-alveolar CHX dressings for the reduction of postoperative alveolar osteitis. (ORAL SURC ORAL MED ORAL PATHOL 1992;73:383-8)


ostextraction alveolar osteitis (AO) is a relatively common local complication that can occur after any tooth extraction in the permanent dentition.lm4 After the surgical removal of third molar teeth from the mandible, the incidence of A0 has been reported to occur in up to 30% of such surgical sites, depending on the factors used to identify this condition.‘, 3 Clinically, postoperative: discomfort can range from simple local inflammation to classic AO, including haliSupported by the DOW’S Institute for Dental Research and the University of Iowa. College of Dentistry. Preliminary report presented at the annual meeting of the American Academy of Oral alnd Maxillofacial Surgery, Sept. 9, 1989, San Francisco, Calif. aProfessor, Department of Oral Pathology, Radiology, and Medicine, University of Iowa College of Dentistry. bAssistant Professor, Department of Oral and Maxillofacial Surgery, University of Iowa College of Dentistry. CResident, Oral and Maxillofacial Surgery, Medical University of South Carolina. din private practice, Clinton, Iowa. 7/17/30287

tosis, regional trismus, and dull throbbing pain. A variety of causes have been suggested for unusual postoperative discomfort and AO, including foreign body responses,4, 5 organic disease,4>6 nutritional factors,7-9 drug therapy,tO surgical technique,2r 4, It, I2 and poor postoperative care.t3, l4 However, the strongest body of evidence points to the role of microbial inhabitants of the oral cavity, belonging specifically to the genus Treponema, and their possible role in causing premature clot lysis. 2, I53l6 The reduction of normal oral flora before oral surgery has been shown to mitigate postextraction symptoms.17>I* Consistent with the strongly suspected microbial pathogenesis of AO, a variety of antibacterial therapeutic modalities have been studied in clinical trials to determine an acceptable preventive routine for use after extraction.‘9-26 Of particular interest is the past use of chlorhexidine (CHX) as an antimicrobial mouthrinse.25-33 CHX digluconate (a polybiguanide) is water soluble and readily dissociates, releasing the positively


Fotos et al.


March 1992

charged CHX at physiologic pH. The bacteriocidal effect of the drug is due to cationic molecular binding to extramicrobial complexes and negatively charged microbial cell walls. This has a net effect of altering the osmotic equilibrium of the cell, resulting in electrolyte loss followed by cell lysis.34-35The safety of CHX use in laboratory animals and in human beings has been well documented. This agent is poorly absorbed after oral administration, is well tolerated after parenteral administration, and exhibits minimal percutaneous absorption, with 90% being excreted in feces and the remainder eliminated through the urinary tract. Extrapolation of experimental data from rodent studies suggestthat the median lethal dose in human beings for CHX is approximately 126,000 mg.37The daily use of mouthrinses for as long as 2 years has not demonstrated any significant hematologic or immunologic changesin healthy human subjects.38 Furthermore, investigations into the mutagenic potential of CHX with rodent models at CHX concentrations 200 times the chemically therapeutic concentration used in oral rinse therapy have also failed to provide sufficient reason for concern.37M40 The broad antimicrobial spectrum of CHX is enhanced through its ability to bind to mucous membranes and to be subsequently released during a 12hour period.3’, 4* Now commercially available as an oral rinse in a 0.12% concentration, CHX has been suggestedfor the treatment of a wide variety of oral conditions including aphthous ulcers, sore mouth as a result of dentures, and gingivostomatisis; as a pronhylaxis in immunocompromised persons; and as an active component of periodontal dressings.29-34T 42-4s The primary disadvantages of CHX when used as an oral cavity includes the bitter taste and the potential for staining the dentition. Additionally, delays in wound healing have been reported with CHX concentrations greater than 0.2%, which suggeststhat in clinical applications CHX should be used at dilutions of 0.2% or less.46,47 Several studies have examined the use of CHX as an adjunctive treatment in periodontal therapy and to reduce postsurgical complications.3’, 34,43,48,49 The use of 0.12% CHX as a preoperative rinse before dental extractions also has been shown to transiently reduce both the total oral microflora and the number of postoperative complications, when usedin conjunction with systemic antibiotic therapy.25Studies on inflammatory exudates accompanying wound sites have shown reductions in leukocytes when CHX was used as a surgical irrigant. 5oInvestigations into the effects of CHX on alveolar bone have shown inhibition of resorption in rodent models.51$52CHX irrigation of periodontal defects produced in the root bifurcation of

posterior teeth of dogs aiso have demonstrated no adverse effect on connective tissue repair or alveolar bone regeneration.53A recent study comparing CHX with a surfactant (cetylpyridinium)-containing antimicrobial has also confirmed previous findings indicating the value of CHX for reducing postextraction A0.28 It has been suggestedthat a more direct application of CHX to the surgical site may produce a greater reduction of postoperative complications such as AO.S4 The potential for direct toxic or inflammatory responsesto CHX when placed in extraction sites has not been well studied, although a recent report has described six casesof immediate hypersensitivity reactions to CHX after topical dermal application.55 Therefore this investigation was designed to explored the benefits of CHX placement into postextraction sites immediately after surgery, to assessthe benefits of intra-alveolar delivery for reducing postoperative discomfort. MATERIAL


Seventy patients seen at the University of Iowa College of Dentistry for elective mandibular third molar removal participated in this study. All subjects were fully informed as to the purpose and procedures planned and any perceived risks. All study participants were assuredthat any information gained about them would be kept completely confidential and not affect their dental treatment, according to the institutional guidelines for the use of human subjects. Medical histories were closely examined for the purpose of excluding persons who were medically compromised by systemic diseasesor medications. Patients seenfor bilateral mandibular third molar removal were selected from the general patient population at the college of dentistry. All patients seenfor removal of impacted teeth were asymptomatic at the time of surgery and had no acute inflammation or infection at the surgical sites. The seven participating oral and maxillofacial surgeonswere given two solutions to use for each case,one containing 2 ml of normal saline solution (0.9%) and the other containing either of two CHX concentrations (0.1% or 0.2%) diluted in pyrogen-free sterile water (Sigma Chemical Co., St. Louis, MO.). These were furnished in paired sterile single-dosevials, with each pair coded as to the identity of its contents (double-blind format). In a split-mouth placebo-controlled experimental design, each subject was treated at one extraction site with a saline solution control whereas the other site received CHX. Immediately after each extraction, the solutions were absorbed onto a 1 cm gelatin sponge (Gelfoam; Henry Schein Inc., Port Washing-


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Surgeon handedness Right Left Case difficulty Uncomplicated Mild difficulty Modera.te difficulty Severe difficullty Surgical site Right more difficult Left more dithcult Surgeon f.requency Surgeon 1 Surgeon 2 Surgeon 3 Surgeon 4 Surgeon 5 Surgeon 6 Surgeon 7 Surgical time (nun): Control site 45 Surgical time (nun): CHX site 45


Table II. Correlation

Table I. Surgical variables Variable



coefficients between patient and surgical variables and surgical site discomfort

85 15 19 71

36 64 4 40 13 11 13 11 8 2 45 34 19

41 32 19

*n = 70 subjects, 14C1surgical sites.

ton, N.Y.) and placed into the surgical defects, followed by closure with sutures for retention. Identical po;stoperative instructions, provided for each test subject after surgery, consisted of abstention from smoking, the use of saline solution rinses, and a soft diet for 48 hours. Evaluation of the postsurgical benefits obtained through the use of each solution was assessedon the basis of a subjective rating (by the patient) of pain intensity and local inflammation, measured on a continuous scale of 0 through 5; lower scores denote less severe signs and symptoms. Postoperative signs and symptoms were also monitored and noted by the surgeons, and included pain, trismus, swelling, erythema, lymphadenopathy, and clot formation to sockNetgranulation characteristics. Scores were recorded by participating surgeons for a period of 5 days postoperatively for each extraction site on each patient. Secondary patient and surgical variables were also monitored to assure study validity. These included age,, sex, and race, and identity of surgeon, dominant handedness of the surgeon, surgical time, surgical site, and case difficulty (angle-position classification of the impaction, proximity to critical structures, difficulty in obtaining hemostasis, and

Variable Patient variables Sex Race Age Surgeon variables Surgical time at control site Surgical time at CHX site Surgeon handedness Operating surgeon Site difficulty Case difficulty


0.05 -0.15 -0.10

-0.22 -0.09 0.01



-0.16 0.15 0.14 -0.06 -0.29*

0.22 0.10 0.25 -0.11 0.25

*Significant negative correlation at p < 0.05, where n = 140.

unusual root curvature), which were all ranked by scores of 1 to 4. A comparison of postoperative signs and symptoms between placebo (saline solution-treated) sites and the CHX test sites at either concentration was carried out with a chi-square analysis (SAS, SAS Institute, Cary, N.C.). The difference between the two CHX concentrations was analyzed by Student’s t test (SAS). Secondary patient variables and surgical variables were evaluated with a Pearson product-moment correlation (SAS). RESULTS

The study population had a male/female ratio of approximately 1:2, a mean age of 22 years, and a median age of 30 years. Race was predominantly white (93%), and five patients were of Asian descent. Table I lists the percentages of patients or surgical sites falling under each surgical variable. Most surgeons were right handed, and left-sided surgical sites were generally perceived as more difficult procedures (64%). An comparison of mean scores across control and medicated sites reported by each surgeon were also compared. These means ranged from 1.1 to 3.2 and were not found to be significantly different. The procedure times for control and medicated sites were similar. No patient variable showed a significant correlation with either control or medicated site discomfort (Table II). There was a moderate, significant negative correlation (-0.29) between the surgical variable, case difficulty, and control site discomfort (p < 0.05) (Table II). No other surgical variables exhibited significant relationships to either control or medicated sites. Table III shows that no significant difference


Fotos et a/.



March 1992

Table III. Postoperative complications between saline solution- and CHX-treated

I Medication Sterile saline 0.9% CHX 0.1% Sterile saline 0.9% CHX 0.2%


Mean discomfort* score {SD) 1.85 2.11 2.16 1.62

21 43

*Mean discomfort score range is 0 to 5, with 0 = no discomfort tSignificant difference by E &t (p < 0.005).

(1.58) (1.67) (1.64) (1.43)

third molar extraction sites

Mean difference

0.25 -0.53

p value

0.182 0.002t

and 5 = severe discomfort.

existed between the control sites that accompanied either CHX concentration. When both CHX medication groups (0.1% and 0.2%) were combined, no significant difference in postoperative discomfort was observed. The same was true when control site discomfort was compared with medicated sites treated with the lower CHX concentration (0.1%). However, the higher concentration (0.2%) resulted in significantly less discomfort (1.62) than the untreated control sites (2.16) (JJ < 0.005). DlSCUSSlON Many techniques have been advocated for the prevention of postoperative complications after third molar removal. Numerous clinical investigators have advocated the use of oral rinses, socket packing, intra-alveolar placement of medicaments or antibiotics, systemic antibiotics, ointments, and so forth. None of these procedures are without their own morbidity, nor are any so effective that their use has eliminated the presence of AO. This study has addressed the prevention of A0 on the assumption that its etiology is predominantly microbial.2> 15,t6 In view of past applications of antimicrobial agents for the treatment of oral diseases, the use of CHX as an intrasulcular dressing logically follows the recent clinical studies that suggest that such agents should be used with a vehicle and placed direct!y into the socket after dental extractions.28, 54 The intrasulcular placement of CHX obviates two of the potential problems in using this agent: its bitter taste and its potential for staining the dentition. Because the etiology of A0 remains somewhat controversial, the experimental design controlled for both patient and surgical variables that can be related to the frequency of complications associated with third molar removal. Attention was also taken to prevent potential bias induced by biologic variation and differences in individual pain perception, through the use of a split-mouth design for each CHX concentration used. Such considerations are especially important in sample sizes less than 100. In this research none of the patient surgical variables analyzed signif-

icantly contributed to the observed benefits obtained with 0.2% CHX-medicated sites. Interestingly, the 0.1% CHX concentration did not significantly reduce postoperative discomfort whereas the use of the higher 0.2% concentration was significantly efficacious in reducing these symptoms and often alleviating pain 24 to 48 hours sooner than control sites in the same patient (descriptive data not shown). The negative correlation between control sites and case difficulty also infers that the surgical sites receiving CHX were, on balance, the more difficult surgical procedures. One may speculate that a higher concentration of CHX might provide an even greater benefit. However, in vitro and in vivo studies have demonstrated that CHX in high concentrations is a cytotoxin and can produce delays in wound granulation and healing, respectively.46> 47,56,j7 F or these reasons the use of this agent at concentrations greater than 0.2% may require further experimental justification before human trials. Alternatively, one must consider that the total drug volume employed in this study was relatively low (2 ml) and that both the concentration and volume of CHX that remains in the wound defect are expected to decrease after placement, because of the local effects of salivary influx and intrasocket hemorrhage. Therefore the true drug delivery at the surgical site remains quantitatively vague after initial hemostasis (perhaps 30 minutes postoperatively). An additional area that requires further consideration is the use of gelatin sponge as the absorptive vehicle for CHX. Although essentially an inert material, several problems related to this material make it less than ideal for use in intra-alveolar CHX delivery. Gelatin sponge has a degree of hydrophobicity that precludes efficient absorption of CHX before intraalveolar placement. In addition, its structured (preshaped) form does not allow for passive placement to the full depth of the socket. A more appropriate vehicle may be microfibrillar or sponge bovine collagen. Future studies are currently under way to evaluate these alternatives further.


Volume 73 Number 3

The efficacy of CHX cannot be fully assessedas an adjunctive agent in the prevention of A0 on the basis of this study. Larger numbers of patients must be treated with tlhe agent, and the results of this study replicated, before any long-term conclusions can be rendered on its use as an intra-alveolar dressing. However, the (data indicate that CHX holds promise as an intra-alveolar antimicrobial medicament for the reduction of postoperative AO. The use of CHX in combination with antibiotics or anti-inflammatory agents for intra-alveolar application may also deserve future evaluation in clinical designs similar to that employed in this study, to develop the most effective combination possible. We express gratitude to Drs. Kirk L. Fridrich, Bradly T. Porter, Scott A. Preisller, Bruce E. Rotter, Robert A. Rudman, Patrick J. Vezea.u, and John M. Wise for their interest and clinical participation, which helped make this research possible.

REFERENCES 1. Schow SR. Evaluation

of postoperative localized osteitis in mandibular third molar surgery. ORAL SURG ORAL MED ORAL



2. Birn H. Etiology and pathogenesis of fibrinolytic alveolitis. Int J Oral Surg 1973;2:211-63. 3. Lilly GE, Osbon DB, Rae1 EM, et al. Alveolar osteitis associated with man’dibular third molar extractions. J Am Dent Assot 1974;88:802-6. MacGregor NJ. Etiology of dry sockets: a clinical investigation. Br J Oral Surg 1968;6:49-58. Eman VH. The dry socket problem. J Oral Surg 1944;2:15866. Bonnette GE, Arentr RE. Raynaud’s disease and extraction wound healing. J Oral Surg 1968;26:185-7. Failo PS. Proteolytic enzyme treatment for the necrotic alveolar socket (dry socket). ORAL SURG ORAL MED ORAL PATHOL 1948;1:608-11. 8. Molt FF. Diet as a factor in healing. J Am Dent Assoc 1936;23:1442-6. 9. Khosla VM, Gough JE. Evaluation of three techniques for the management of postextraction third molar sockets. ORAL SURG ORAL M.ED ORAL PATHOL


10. Catellani JE. Review of factors contributing to dry socket through enhanced fibrinolysis. J Oral Surg 1979;37:42-6. 11. Ailing CC, Kerr DA. Post-extraction osteomyelitic syndrome. J Oral Surg 1957;15:3-11. 12. MacGregor AJ, Hart P. Effects of bacteria and other factors on pain and swelling arfter removal of ectopic mandibular third molars. J Oral Surg 1967;27:174-9. 13. Winter L. Local anesthesia and exodontia. Dent Cosmos 1931.73.545-55. / . 14. Williams AP. Exodontia relevant to the general practitioner. J Am Dent Assoc 1935;22:239-43. 15. Nitzan DW. On the genesis of “dry sockets,” J Oral Maxillofat Surg 1983;41:706~-10. 16. Nitzan DW, Sperry JF, Wilkins TD. Fibrinolytic activity of oral anaerobic bacteria. Arch Oral Biol 1978;23:465-70. 17. Brown LR, Merrill S,S, Allen RE. Microbiologic study of intraoral wounds. J Oral Surg 1970;28:89-95. 18. MacGregor AJ, Hart P. Bacteria of the extraction wound. J Oral Surg 1970;28:885-7. 19. Scully JR. Influence of polylactic acid, mesh on the incidence



of localized osteitis [Master’s thesis]. Iowa City: The University of Iowa, 1980. 20. Boyne PJ, Kruger GO. Topical implantation of oxytetracycline cones in extraction sockets. J Am Dent Assoc 1962;64:224-35. 21. Hall HD, Bildman BS, Hand CD. Prevention of dry socket with local application of tetracycline. J Oral Surg 1971;29: 35-7. 22. Mourfield WR, Barron JM. Clinical evaluation of erythromytin dental cones in oral surgery. ORAL SURG ORAL MED ORAL PATHOL


23. Ostrander FD, Hartmann FW. Local use of sulfonamides. J Am Dent Assoc 1942;29:1051-64. 24. Fridrich KL. Alveolitis sicca dolorosa following surgical removal of mandibular third molars [Master’s thesis]. Iowa City: The University of Iowa, 1987. 25. Krekmanov L, Nordenram A. Postoperative complications after surgical removal of mandibular third molars: effects of penicillin V and chlorhexidine. Int J Oral Maxillofac Surg 1986;15:25-9. 26. Jokinen MA. Prevention of postextraction bacteremia by local prophylaxis. Int J Oral Surg 1978;7:450-2. 27. Tjernberg A. Influence of oral hygiene measures on the development of alveolitis sicca dolorosa after surgical removal of mandibular third molar. Int J Oral Surg 1979;8:430-4. 28. Berwick JE, Lessin ME. Effects of chlorhexidine gluconate oral rinse on the incidence of alveolar osteitis in mandibular third molar surgery. J Oral Maxillofac Surg 1990;48:444-8. 29. Abby M, Hunter L. The effects of a 0.2% chlorhexidine gluconate mouthrinse on plaque, toothstaining and Candida in aphthous ulcer patients. J Clin Periodontol 1987;14:267-73. 30. Addy M, Tapper-Jones L, Seal M. Trial of astringent and antibacterial mouthwashes in the management of recurrent aphthous ulceration. Br Dent J 1974;136:452-5. 31. O’Neal TCA. The use of chlorhexidine mouthwash in the control of gingival infammation. Br Dent J 1976;141:276-80. 32. McGaw WT, Belch A. Oral Complications of acute leukemia: prophylactic impact of a chlorhexidine mouth rinse regimen. ORAL SURG ORAL MED ORAL PATHOL


33. Ferretti GA, Ash RC, Brown AT. Chlorhexidine for prophylaxis against oral infections and associated complications in patients receiving bone marrow transplants. J Am Dent Assoc 1987;114:461-7. 34. Greenstein G, Berman C, Jaffen R. Chlorhexidine an adjunct to periodontal therapy. J Periodontol 1986;57:370-7. 35. Bonesvoll P. Oral pharmacology of chlorhexidine. J Periodont Res 1977;12:49-65. 36. Hugo WB, Longworth AR. Some aspects of the mode of action of chlorhexidine J Pharm Pharmacol 1964; 16:655-62. 37. Case DE. Safety of Hibitane 1. Laboratory experiments. J Clin Periodontol 1977;4:66-72. 38. Schiott CR, Loe H, Briner, WW. Two-year oral use of chlorhexidine in man: effect on various medical parameters. J Periodont Res 1976;11:158-64. 39. National Cancer Institute. Carcinogenesis. Technical support series No 189, 1979. 40. Schmidt AB, Sussmuth R, Lingens F. The reaction of the mutagen 1,l ‘-hexamethylene-bis[(5-p-chlorophenyl)-biguanide] with cysteine and guanosine. Biochem Biophys Acta 1982; 699:149-54. 41. Rolla G, Loe H, Schiott CR. The affinity of chlorhexidine for hydroxyapatite and salivary mucins. J Periodont Res 1970; 5:90-5. 42. Shaw WC, Addy M, Griffiths S, et al. Chlorhexidine and traumatic ulcers in orthodontic patients. Eur J Orthod 1984; 6:137-40. 43. Pluss EM, Engelberger PR, Rateitschak KH. Effect of chlorhexidine on dental plaque formation under periodontal pack. J Clin Periodontol 1975;2:136-42. 44. Buddtz-Jorgensen E. Hibitane in the treatment of oral candidiasis. J Clin Periodontol 1977;4:117-28. 45. Gjermo P. Chlorhexidine in dental practice. J Clin Periodonto1 1974;1:143-52.


Fotos et al.

46. Harvey CA, Squier CA, Hall BK. Effects of chlorhexidine on the structure and permeability of hamster cheek pouch mucosa. J Periodontol 1984;55:608-14. 47. Lang NP, Grossmann KR. Optimal dosage of chlorhexidine digluconate in chemical plaque control when applied by the oral irrigator. J Clin Periodontol 1981;8:189-202. 48. Bassetti C, Kallenberger A. Influence of chlorhexidine rinsing on healing of oral mucosa and osseous lesions. J Clin Periodontol 1980;7:443-56. 49. Langebaek J, Bay L. The effect of chlorhexidine mouthrinse on healing after gingivectomy. Stand J Dent Res 1976;84:224-8. 50. Knuutilla MLE, Paunio KU, Mielitynen H. Effect of chlorhexidine gluconate on acute nonmicrobial inflammation reaction. J Periodontol 1978;49:96-101. 5 1, Leonard EP, Reese WV, Benson CL, et al. Decreased alveolar bone resorption in rice rats treated with chlorhexidine and stannous fluoride. J Periodont Res 1980;15:650-4. 52. Messer HH, Douglas WH. Inhibition by chlorhexidine of alveolar bone loss in mice. J Periodont Res 1980;15:646-9. 53. Bogle G, Rathburn E, Oliver R, et al. Effect of postoperative



55. 56.



use of chlorhexidine on regeneration of bifurcation defects of dogs. J Periodont Res 1974;9:127-33. Hall HD. Effects of chlorhexidine gluconate oral rinse on the incidenceof alveolar osteitis in mandibular third molar surgery IDiscussionl. J Oral Maxillofac Surg 1990:48:449. bkano M, Nomura M, Hata S, et al.-Anapdylactic symptoms due tochlorhexidinegluconate. Arch Dermatol1989;125:50-2. Paunio KU, Knuuttila M, Mielityinen H. The effect of chlorhexidine gluconate on the formation of experimental granulation tissue. J Periodontol 1978;49:92-5. Fotos PG, Crout RJ, Matheny A, et al. The effect of periodontal antimicrobial agents on human gingival cell viability. J Dent Res 1988;67:1284.

Reprint requests: Pete G. Fotos, DDS, MS, PhD Department of Oral Pathology, Radiology, and Medicine University of Iowa College of Dentistry Iowa City, IA 52242

Evaluation of intra-alveolar chlorhexidine dressings after removal of impacted mandibular third molars.

Chlorhexidine gluconate (CHX) has been investigated for its possible benefit in the prevention of alveolar osteitis complicating third molar removal. ...
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