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Effectiveness of 0.2% chlorhexidine gel and a eugenol-based paste on postoperative alveolar osteitis in patients having third molars extracted: a randomised controlled clinical trial
YBJOM-4561; No. of Pages 5
ARTICLE IN PRESS Available online at www.sciencedirect.com
British Journal of Oral and Maxillofacial Surgery xxx (2015) xxx–xxx
Effectiveness of 0.2% chlorhexidine gel and a eugenol-based paste on postoperative alveolar osteitis in patients having third molars extracted: a randomised controlled clinical trial James Solomon Jesudasan ∗ , P.U. Abdul Wahab, M.R. Muthu Sekhar Saveetha Dental College, Department Oral & Maxillofacial Surgery, 162 Poonammallee High Road, Chennai 600077, India Accepted 21 June 2015
Abstract The aim of this study was to compare the effect of application of 0.2% chlorhexidine gel, a eugenol-based paste, together with a control group on the postoperative incidence of alveolar osteitis in patients having third molars extracted. A total of 270 patients who had this procedure at the Dept of Oral and Maxillofacial Surgery, Saveetha Dental College and who met the inclusion criteria were enrolled in the study and divided into 3 groups: the first had a 0.2% chlorhexidine-based gel applied to the alveolar socket once after extraction; the second had a eugenol-based paste applied to the alveolar socket once after extraction; and the third group acted as controls, with no treatment. The incidence of alveolar osteitis was recorded for 7 days. We also recorded postoperative pain, inflammation, infection, and wound healing. Nine of the control group (10%) and 2 (2%) of the chlorhexidine group developed alveolar osteitis on the seventh postoperative day. The overall incidence (11/270) was 4%, which is less than reported elsewhere. The distribution of alveolar osteitis among the 3 groups was significant (p= 0.002), with the eugenol group having no cases. The chlorhexidine group showed less incidence of alveolar osteitis than other reported studies and also less pain, inflammation, infection, and better wound healing than the control group. We conclude that eugenol was the better of the 2 interventions. © 2015 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
Keywords: Alveolar osteitis; Prevention of alveolar osteitis; Dry socket; Intra-alveolar medication
Introduction One of the most common postoperative complications after the extraction of permanent teeth is a condition known as dry socket. This term has been in use since 1896, when it was first described by Crawford.1 Since then several other terms have been used, including alveolar osteitis, localised
∗ Corresponding author at: 162 Poonammallee High Road Department Oral & Maxillofacial Surgery Saveetha Dental College. Chennai.600077. India. Tel.: +044-26801581-4. E-mail addresses: [email protected] (J.S. Jesudasan), [email protected] (P.U.A. Wahab), [email protected] (M.R.M. Sekhar).
osteitis, postoperative alveolitis, alveolalgia, alveolitis, sicca dolorosa, and fibrinolytic alveolitis. Birn2 labelled the complication fibrinolytic alveolitis, which is the most accurate of the terms, but also the least used. The condition has generally been characterised by delayed healing associated with degradation of clot, and is usually accompanied by persistent, radiating, pain postoperatively in and around the extraction site that is not easily relieved by analgesics. It can be a burden for both patients and surgeons,3 and may result in a loss of productivity because at least 45% of patients require multiple visits to the surgeon. It can also be costly in terms of the clinic time required to manage the patient’s symptoms.4,5
http://dx.doi.org/10.1016/j.bjoms.2015.06.022 0266-4356/© 2015 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: Jesudasan JS, et al. Effectiveness of 0.2% chlorhexidine gel and a eugenol-based paste on postoperative alveolar osteitis in patients having third molars extracted: a randomised controlled clinical trial. Br J Oral Maxillofac Surg (2015), http://dx.doi.org/10.1016/j.bjoms.2015.06.022
YBJOM-4561; No. of Pages 5
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ARTICLE IN PRESS J.S. Jesudasan et al. / British Journal of Oral and Maxillofacial Surgery xxx (2015) xxx–xxx
Rationale for this trial Many authors have advocated different methods of treating alveolar osteitis, some of whom have promoted dressings that contain eugenol to prevent its development,6–8 and some who have shown that that the use of 0.12% chlorhexidine before and after extraction decreases its incidence after removal of mandibular third molars.8–11 Despite many years of research, however, little progress has been made and so a study with a large enough sample and standard outcome measures is warranted.
Patients and methods Design of the study We selected a power of 90% and a probability of less than 0.05 to be significant. We calculated the sample size using G power software and concluded that a final minimum sample size of 90 patients in each group would be satisfactory. This double blind, randomised, controlled trial was done between January 2012 and September 2013 after review and ethical clearance by the institutional ethics committee. Informed consent was obtained from all the participants. Patients with clinical and radiographic evidence of impacted mandibular third molars were included. Patients with any systemic disease, history of epilepsy, smokers, those who misused alcohol, women taking contraceptives, patients with infections or who were taking analgesics 1 week preoperatively, those known to be allergic to chlorhexidine or eugenol, and any other condition or disease that contraindicated extraction were excluded. The 270 patients were divided into 3 equal groups of 90 each by block randomisation. Lots were picked to decide the allocation of the patients. Operative technique Local anaesthetic comprised 1% or 2% lignocaine hydrochloride 2 ml with 1:200,000 units adrenalin. Bone guttering was done as and when necessary with the aid of a saline-cooled bur. The tooth was raised, extracted in full, or split as and when necessary according to the habit of the operating surgeon, and 0.2% chlorhexidine gel, or Alvogel, or nothing placed in the extraction socket. The socket was then sutured. Patients were discharged taking metronidazole 400 mg three times daily for 3 days and Zerodol (aceclophenac + serratiopeptidase, Intas Pharm, Ahmedabad, India) twice daily for 3 days, and were reviewed on postoperative days 1, 3, and 7. Criteria for diagnosis and collection of data For the diagnosis of alveolar osteitis, 2 of 3 criteria must be met.12 These are: increased throbbing pain between
postoperative days 3 and 5 that is not relieved by analgesics; the presence of dark fragments from a resorbed blood clot on irrigation of a painful extraction socket; and substantial alleviation of pain with a reduction on the visual analogue scale (VAS for pain 1-10) of more than 3 points within 10 minutes of application of a dressing to the dry socket. Infection and epithelialisation were measured as described by Aronovich et al.12 Analysis of data The significances of differences among the data were evaluated with the help of SPSS (version17, SPSS Inc, Chicago, IL, USA). One way analysis of variance (ANOVA) was used for mean pain values, the chi square test for the incidence of alveolar osteitis, and the repeated measures ANOVA was used for pain.
Results We studied a total of 270 patients (160 male and 110 female). The mean (SD) age in the control group was 28 (7) years, in the chlorhexidine group 28 (6) years, and in the eugenol group 29 (8) years. The mean ages did not differ significantly (p=0.392), nor did the level, class, or angulation of the tooth. Wound healing was poorest in the control group on day 7 with a mean score of 2.51 compared to 1.69 and 1.32 in the chlorhexidine and eugenol groups (p<0.001, Table 1). Eleven of the 270 patients (4%) developed alveolar osteitis on postoperative day 7 (Table 2) and its distribution among the 3 groups was significant(p< 0.002) with there being none in the eugenol group. The incidence of infection followed a similar pattern to that of osteitis and was less than that reported in other papers. Postoperative pain was worst in the control group, with the highest mean (SD) VAS score on day 1 (Tables 1 and 3). Day 3 showed a mean VAS score of only 1.62 in the eugenol group as compared to 3.33 and 5.4 in the chlorhexidine and control groups. This continued to be the pattern on day 7 groups (p <0.001). Inflammation on day 1 did not differ significantly, but on days 3 and 7 there were significant differences among the 3 groups (p<0.001, Table 4). Table 5 shows the withinsubjects and between-subjects effects of the analysis of pain scores.
Discussion Most patients are not aware of the complications of surgical extraction of wisdom teeth, which prompted us to organise a study to try and solve the problem of alveolar osteitis. We wanted to provide a reasonably cheap and efficient method that could be universally used to avoid it.
Please cite this article in press as: Jesudasan JS, et al. Effectiveness of 0.2% chlorhexidine gel and a eugenol-based paste on postoperative alveolar osteitis in patients having third molars extracted: a randomised controlled clinical trial. Br J Oral Maxillofac Surg (2015), http://dx.doi.org/10.1016/j.bjoms.2015.06.022
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Table 1 Pain and wound healing in the three groups. Variable Pain, day 1: Mean (SD) SE 95% CI of mean Pain, day 3: Mean (SD) SE 95% CI of mean Pain, day 7: Mean (SD) SE 95% CI of mean Wound healing, day 1: Mean (SD) SE 95% CI of mean Wound healing, day 7: Mean (SD) SE 95% CI of mean
Control (n=90)
Chlorhexidine (n=90)
Eugenol (n=90)
Total (n=270)
7.53 (0.64) 0.067 7.4 to 7.67
6.4 (0.49) 0.052 6.30 to 6.50
5.42 (0.54) 0.057 5.31 to 5.54
6.45 (1.03) 0.063 6.33 to 6.58
5.41 (0.91) 0.096 5.22 to 5.60
3.33 (0.81) 0.085 3.16 to 3.50
1.62 (0.63) 0.066 1.49 to 1.75
3.46 (1.74) 0.106 3.25 to 3.66
3.14 (1.36) 0.144 2.86 to 3.43
1.73 (0.93) 0.098 1.54 to 1.93
0.39 (0.58) 0.061 0.27 to 0.51
1.76 (1.51) 0.092 1.57 to 1.94
5.5 (0.60) 0.064 5.37 to 5.63
4.39 (0.56) 0.058 4.27 to 4.51
4.47 (0.58) 0.062 4.34 to 4.59
4.79 (0.77) 0.047 4.69 to 4.88
2.51 (0.69) 0.073 2.37 to 2.66
1.69 (0.66) 0.070 1.55 to 1.83
1.32 (0.49) 0.052 1.22 to 1.43
1.84 (0.80) 0.048 1.75 to 1.94
Table 2 Alveolar osteitis. Alveolar osteitis Day 1: Yes No Day 3: Yes No Day 7: Yes No
Control (n=90)
Chlorhexidine (n=90)
Eugenol (n=90)
Total (n=270)
90
90
90
270
90
90
90
270
9 81
2 88
90
11 259
chi square=12.699; df=2; p<0.02
Table 3 A. Mean (SD) pain scores between groups. Day and range
Control (n=90)
Chlorhexidine (n=90)
Eugenol (n=90)
Total (n=270)
Day 1 Range Day 3 Range Day 7 Range
7.53 (0.64) 6-9 5.41 (0.91) 3-7 3.14 (1.36) 2-7
6.40 (0.49) 6-7 3.33 (0.81) 2-7 1.73 (0.93) 0-8
5.42 (0.54) 4-6 1.62 (0.63) 0-3 0.39 (0.58) 0-3
6.45 (1.03) 4-9 3.46 (1.74) 0-7 1.76 (1.51) 0-8
B. Analysis of Variance Day
df
Mean square
F value
p value
1 3 7
2 2 2
100.459 324.011 170.878
319.486 518.202 167.668
<0.001 <0.001 <0.001
Please cite this article in press as: Jesudasan JS, et al. Effectiveness of 0.2% chlorhexidine gel and a eugenol-based paste on postoperative alveolar osteitis in patients having third molars extracted: a randomised controlled clinical trial. Br J Oral Maxillofac Surg (2015), http://dx.doi.org/10.1016/j.bjoms.2015.06.022
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Table 4 A. Number (%) with inflammation. Inflammation Day 1: Yes No Day 3: Yes No Day 7: Yes No
Control (n=90)
Chlorhexidine (n=90)
Eugenol (n=90)
Total (n=270)
90
90
2 88
2 268 (99)
87 3
43 47
2 88
132 (49) 138 (51)
13 77
2 88
0 90
15 (6) 255 (94)
B. Chi square analysis Day
Chi square
df
p value
1 3 7
4.03 160.702 20.753
2 2 2
0.133 <0.001 <0.001
Table 5 A. Within-subjects effects: pain score (sphericity assumed).
Pain score Pain score intervention group Error (pain score)
Type III sum of squares
df
Mean square
F value
p value
3.53.069 65.183 249.081
2 4 534
1526.535 16.296 0.466
3272.702 34.936
<0.001 <0.001
B. Between-subjects effects - pain score: transformed variable – mean. Source
Type III sum of squares
df
Mean square
F value
p value
Intercept Intervention group Error
12242.223 1125.514 273.930
1 2 267
12242.223 562.757 1.026
11932.531 548.521
<0.001 <0.001
The male:female ratio did not differ significantly and was uniformly distributed among the 3 groups. The incidence of alveolar osteitis (4%) was much less than reported elsewhere.3,5–8 Of the 90 patients in each group, 9 from the control group and 2 from the chlorhexidine group developed were affected. The eugenol group had no cases, and eugenol was therefore the better preventative. There were fewer cases of alveolar osteitis in the chlorhexidine group than in the control group, which is consistent with previous reports. This suggests that chlorhexidine reduces rates of alveolar osteitis by 25% to 80% after the extraction of impacted mandibular third molars .8,11,13,14 The active components of the interventions cited in previous studies have possessed antibacterial and analgesic properties, or a topical anaesthetic, or a combination, that have resulted in reduction in the incidence of alveolar osteitis.3,7 Chlorhexidine has been shown to be a good prophylactic for dry socket alveolitis. In a study by Ragno and Szkutnik,15 0.2% chlorhexidine digluconate mouthwash produced a reduction in alveolar osteitis after extraction of impacted third molars from 160 sites (from 29/80 (36%) to 14/80 (17.5%) in a control group). Bloomer4 reported that the incidence of localised osteitis was 8/100 sockets that were immediately packed (with ¼–inch radiographically-detectable filament gauze that contained 9%
eugenol, 36% balsam of Peru, and 55% petroleum jelly) and 26/100 sockets that were not immediately packed. The overall low incidence of alveolar osteitis in our trial that spanned over 1½ years could be attributed to the fact that all patients were apparently healthy. Smokers,16–19 people who misused alcohol, and women on oral contraceptives13,17,20–22 were also excluded. Surgical expertise and strict asepsis could also have contributed. The incidence of infection followed a similar pattern to that of alveolar osteitis, and this was not commonly reported in other papers, there being 13 cases in the control group and 2 in the chlorhexidine group, with none in the eugenol group. Comparison of the postoperative pain scores showed that eugenol significantly reduced postoperative pain. Given the severe pain and subsequent anxiety of patients with alveolar osteitis, pain relief is the primary goal of treatment. Jorkjend and Skoglund compared the effects of 2 periodontal dressings containing eugenol and 1 dressing without eugenol on postoperative pain after gingivectomy, and found that eugenol had a significant effect in the control of postoperative pain.13 Acemannan (an extract of aloe vera) inhibits the inflammatory process and relieves pain by interfering with the arachidonic acid pathway by way of cyclooxygenase. Eugenol can also inhibit the inflammatory process and provide analgesic
Please cite this article in press as: Jesudasan JS, et al. Effectiveness of 0.2% chlorhexidine gel and a eugenol-based paste on postoperative alveolar osteitis in patients having third molars extracted: a randomised controlled clinical trial. Br J Oral Maxillofac Surg (2015), http://dx.doi.org/10.1016/j.bjoms.2015.06.022
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effects by inhibition of the action of prostaglandins, which significantly reduced postoperative pain compared with the other 2 groups. The changes in inflammation among the 3 groups also differed (Table 4). As mentioned before both chlorhexidine and eugenol seem to possess anti-inflammatory properties and this was evident from our study. The significant difference in infection in the eugenol group can be attributed to the fact that low concentrations of eugenol exert anti-inflammatory and local anaesthetic effects on oral tissue.13 Wound healing did not show a significant difference between the two intervention groups but with the control only. Eugenol showed not only superior pain relief and anti-inflammatory properties but also better wound healing compared with the other 2 groups. We conclude that there seems to be a clear advantage to the use of intra-alveolar medication after extraction of lower third molars, since the results from previous studies concerning the placement of intra-alveolar drugs for the prevention of alveolar osteitis are controversial, their use does not seem to be indicated at the present. We know of no published clinical trial similar to ours that has compared the use of a chlorhexidine gel or a eugenol-based paste placed in the alveolus for the prevention of alveolitis after the extraction of impacted third molars. We can therefore compare our study only with other trials of other products and other presentations of chlorhexidine and eugenol. Chlorhexidine perioperatively has consistently been shown to deliver a substantial reduction in alveolar osteitis and can be a useful intra-alveolar medication when used in gel form as we did. Eugenol has long been used as an effective treatment for dry socket. Eugenol proved to be the most effective of the two interventions not only in relation to the incidence of alveolar osteitis but also the presence of pain, infection, inflammation, and wound healing. We suggest the routine use of eugenol paste (Alvogyl) after extraction of a third molar not only as a preventative measure against alveolar osteitis but also to reduce pain, inflammation, and promote wound healing. Ideally, a specific guideline should be developed from the available scientific evidence on the prophylactic management of alveolar osteitis during dental extractions to benefit general practitioners and oral surgeons in providing optimal patient care. Conflict of Interest We have no conflict of interest. Ethics statement/confirmation of patients’ permission The trial was approved by the Institutional Ethics Committee and The Institutional Research Committee. Each patient gave consent to participation in the trial.
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References 1. Crawford YJ. Dry sockets after extraction. Dental Cosmos 1896;38:929–31. 2. Birn H. Etiology and pathogenesis of fibrinolytic alveolitis (dry socket). International Journal of Oral Surgery 1973;2:211–63. 3. Blum IR. Contemporary views on dry socket (alveolar osteitis): a clinical appraisal of standardization, aetiopathogenesis and management: a critical review. Int J Oral Maxillofac Surg 2002;31:309–17. 4. Bloomer CR. Alveolar osteitis prevention by immediate placement of medicated packing. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2000;90:282–4. 5. Torres-Lagares D, Gutierrez-Perez JL, Infante-Cossio P, et al. Randomized, double-blind study on effectiveness of intra-alveolar chlorhexidine gel in reducing the incidence of alveolar osteitis in mandibular third molar surgery. Int J Oral Maxillofac Surg 2006;35:348–51. 6. Lilly GE, Osbon DB, Rael EM, et al. Alveolar osteitis associated with mandibular third molar extractions. J Am Dent Assoc 1974;88:802–6. 7. Alexander RE. Dental extraction wound management: a case against medicating postextraction sockets. J Oral Maxillofac Surg 2000;58:538–51. 8. Berwick JE, Lessin ME. Effects of a chlorhexidine gluconate oral rinse on the incidence of alveolar osteitis in mandibular third molar surgery. J Oral Maxillofac Surg 1990;48:444–9. 9. Larsen PE. The effect of a chlorhexidine rinse on the incidence of alveolar osteitis following the surgical removal of impacted mandibular third molars. J Oral Maxillofac Surg 1991;49:932–7. 10. Hermesch CB, Hilton TJ, Biesbrock AR, et al. Perioperative use of 0.12% chlorhexidinegluconate for the prevention of alveolar osteitis: efficacy and risk factor analysis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1998;85:381–7. 11. Tjernberg A. Influence of oral hygiene measures on the development of alveolitis sicca dolorosa after surgical removal of mandibular third molars. Int J Oral Surg 1979;8:430–4. 12. Aronovich S, Skope LW, Kelly JP, et al. The relationship of glycemic control to dental extractions. J Oral Maxillofac Surg 2010;68: 2955–61. 13. Jorkjend L, Skoglund LA. Effect of non-eugenol- and eugenol containing periodontal dressings on the incidence and severity of pain after periodontal soft tissue surgery. J Clin Periodontol 1990;17: 341–4. 14. Brekke JH, Bresner M, Reitman MJ. Effect of surgical trauma and polylactate cubes and granules on the incidence of alveolar osteitis in mandibular third molar extraction wounds. J Can Dent Assoc 1986;52:315–9. 16. Ragno Jr JR, Szkutnik AJ. Evaluation of 0.12% chlorhexidine rinse in the prevention of alveolar osteitis. Oral Surg Oral Med Oral Pathol 1991;72:524–6. 17. Larsen PE. Alveolar osteitis after surgical removal of impacted mandibular third molars: identification of the patient at risk. Oral Surg Oral Med Oral Pathol 1992;73:393–7. 18. Sweet JB, Butler DP. Predisposing and operative factors: effect on the incidence of localized osteitis in mandibular third-molar surgery. Oral Surg Oral Med Oral Pathol 1978;46:206–15. 19. Butler DP, Sweet JB. Effect of lavage on the incidence of localized osteitis in mandibular third molar extraction sites. Oral Surg Oral Med Oral Pathol 1977;44:14–20. 20. Schow SR. Evaluation of postoperative localized osteitis in mandibular third molar surgery. Oral Surg Oral Med Oral Pathol 1974;38: 352–8. 21. Johnson WS, Blanton EE. An evaluation of 9-aminoacridine/Gelfoam to reduce dry socked formation. Oral Surg Oral Med Oral Pathol 1988;66:167–70. 22. Barclay JK. Metronidazole and dry socket: prophylactic use in mandibular third molar removal complicated by non-acute pericoronitis. N Z Dent J 1987;83:71–5.
Please cite this article in press as: Jesudasan JS, et al. Effectiveness of 0.2% chlorhexidine gel and a eugenol-based paste on postoperative alveolar osteitis in patients having third molars extracted: a randomised controlled clinical trial. Br J Oral Maxillofac Surg (2015), http://dx.doi.org/10.1016/j.bjoms.2015.06.022
ARTICLE IN PRESS Available online at www.sciencedirect.com
British Journal of Oral and Maxillofacial Surgery xxx (2015) xxx–xxx
Effectiveness of 0.2% chlorhexidine gel and a eugenol-based paste on postoperative alveolar osteitis in patients having third molars extracted: a randomised controlled clinical trial James Solomon Jesudasan ∗ , P.U. Abdul Wahab, M.R. Muthu Sekhar Saveetha Dental College, Department Oral & Maxillofacial Surgery, 162 Poonammallee High Road, Chennai 600077, India Accepted 21 June 2015
Abstract The aim of this study was to compare the effect of application of 0.2% chlorhexidine gel, a eugenol-based paste, together with a control group on the postoperative incidence of alveolar osteitis in patients having third molars extracted. A total of 270 patients who had this procedure at the Dept of Oral and Maxillofacial Surgery, Saveetha Dental College and who met the inclusion criteria were enrolled in the study and divided into 3 groups: the first had a 0.2% chlorhexidine-based gel applied to the alveolar socket once after extraction; the second had a eugenol-based paste applied to the alveolar socket once after extraction; and the third group acted as controls, with no treatment. The incidence of alveolar osteitis was recorded for 7 days. We also recorded postoperative pain, inflammation, infection, and wound healing. Nine of the control group (10%) and 2 (2%) of the chlorhexidine group developed alveolar osteitis on the seventh postoperative day. The overall incidence (11/270) was 4%, which is less than reported elsewhere. The distribution of alveolar osteitis among the 3 groups was significant (p= 0.002), with the eugenol group having no cases. The chlorhexidine group showed less incidence of alveolar osteitis than other reported studies and also less pain, inflammation, infection, and better wound healing than the control group. We conclude that eugenol was the better of the 2 interventions. © 2015 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
Keywords: Alveolar osteitis; Prevention of alveolar osteitis; Dry socket; Intra-alveolar medication
Introduction One of the most common postoperative complications after the extraction of permanent teeth is a condition known as dry socket. This term has been in use since 1896, when it was first described by Crawford.1 Since then several other terms have been used, including alveolar osteitis, localised
∗ Corresponding author at: 162 Poonammallee High Road Department Oral & Maxillofacial Surgery Saveetha Dental College. Chennai.600077. India. Tel.: +044-26801581-4. E-mail addresses: [email protected] (J.S. Jesudasan), [email protected] (P.U.A. Wahab), [email protected] (M.R.M. Sekhar).
osteitis, postoperative alveolitis, alveolalgia, alveolitis, sicca dolorosa, and fibrinolytic alveolitis. Birn2 labelled the complication fibrinolytic alveolitis, which is the most accurate of the terms, but also the least used. The condition has generally been characterised by delayed healing associated with degradation of clot, and is usually accompanied by persistent, radiating, pain postoperatively in and around the extraction site that is not easily relieved by analgesics. It can be a burden for both patients and surgeons,3 and may result in a loss of productivity because at least 45% of patients require multiple visits to the surgeon. It can also be costly in terms of the clinic time required to manage the patient’s symptoms.4,5
http://dx.doi.org/10.1016/j.bjoms.2015.06.022 0266-4356/© 2015 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: Jesudasan JS, et al. Effectiveness of 0.2% chlorhexidine gel and a eugenol-based paste on postoperative alveolar osteitis in patients having third molars extracted: a randomised controlled clinical trial. Br J Oral Maxillofac Surg (2015), http://dx.doi.org/10.1016/j.bjoms.2015.06.022
YBJOM-4561; No. of Pages 5
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ARTICLE IN PRESS J.S. Jesudasan et al. / British Journal of Oral and Maxillofacial Surgery xxx (2015) xxx–xxx
Rationale for this trial Many authors have advocated different methods of treating alveolar osteitis, some of whom have promoted dressings that contain eugenol to prevent its development,6–8 and some who have shown that that the use of 0.12% chlorhexidine before and after extraction decreases its incidence after removal of mandibular third molars.8–11 Despite many years of research, however, little progress has been made and so a study with a large enough sample and standard outcome measures is warranted.
Patients and methods Design of the study We selected a power of 90% and a probability of less than 0.05 to be significant. We calculated the sample size using G power software and concluded that a final minimum sample size of 90 patients in each group would be satisfactory. This double blind, randomised, controlled trial was done between January 2012 and September 2013 after review and ethical clearance by the institutional ethics committee. Informed consent was obtained from all the participants. Patients with clinical and radiographic evidence of impacted mandibular third molars were included. Patients with any systemic disease, history of epilepsy, smokers, those who misused alcohol, women taking contraceptives, patients with infections or who were taking analgesics 1 week preoperatively, those known to be allergic to chlorhexidine or eugenol, and any other condition or disease that contraindicated extraction were excluded. The 270 patients were divided into 3 equal groups of 90 each by block randomisation. Lots were picked to decide the allocation of the patients. Operative technique Local anaesthetic comprised 1% or 2% lignocaine hydrochloride 2 ml with 1:200,000 units adrenalin. Bone guttering was done as and when necessary with the aid of a saline-cooled bur. The tooth was raised, extracted in full, or split as and when necessary according to the habit of the operating surgeon, and 0.2% chlorhexidine gel, or Alvogel, or nothing placed in the extraction socket. The socket was then sutured. Patients were discharged taking metronidazole 400 mg three times daily for 3 days and Zerodol (aceclophenac + serratiopeptidase, Intas Pharm, Ahmedabad, India) twice daily for 3 days, and were reviewed on postoperative days 1, 3, and 7. Criteria for diagnosis and collection of data For the diagnosis of alveolar osteitis, 2 of 3 criteria must be met.12 These are: increased throbbing pain between
postoperative days 3 and 5 that is not relieved by analgesics; the presence of dark fragments from a resorbed blood clot on irrigation of a painful extraction socket; and substantial alleviation of pain with a reduction on the visual analogue scale (VAS for pain 1-10) of more than 3 points within 10 minutes of application of a dressing to the dry socket. Infection and epithelialisation were measured as described by Aronovich et al.12 Analysis of data The significances of differences among the data were evaluated with the help of SPSS (version17, SPSS Inc, Chicago, IL, USA). One way analysis of variance (ANOVA) was used for mean pain values, the chi square test for the incidence of alveolar osteitis, and the repeated measures ANOVA was used for pain.
Results We studied a total of 270 patients (160 male and 110 female). The mean (SD) age in the control group was 28 (7) years, in the chlorhexidine group 28 (6) years, and in the eugenol group 29 (8) years. The mean ages did not differ significantly (p=0.392), nor did the level, class, or angulation of the tooth. Wound healing was poorest in the control group on day 7 with a mean score of 2.51 compared to 1.69 and 1.32 in the chlorhexidine and eugenol groups (p<0.001, Table 1). Eleven of the 270 patients (4%) developed alveolar osteitis on postoperative day 7 (Table 2) and its distribution among the 3 groups was significant(p< 0.002) with there being none in the eugenol group. The incidence of infection followed a similar pattern to that of osteitis and was less than that reported in other papers. Postoperative pain was worst in the control group, with the highest mean (SD) VAS score on day 1 (Tables 1 and 3). Day 3 showed a mean VAS score of only 1.62 in the eugenol group as compared to 3.33 and 5.4 in the chlorhexidine and control groups. This continued to be the pattern on day 7 groups (p <0.001). Inflammation on day 1 did not differ significantly, but on days 3 and 7 there were significant differences among the 3 groups (p<0.001, Table 4). Table 5 shows the withinsubjects and between-subjects effects of the analysis of pain scores.
Discussion Most patients are not aware of the complications of surgical extraction of wisdom teeth, which prompted us to organise a study to try and solve the problem of alveolar osteitis. We wanted to provide a reasonably cheap and efficient method that could be universally used to avoid it.
Please cite this article in press as: Jesudasan JS, et al. Effectiveness of 0.2% chlorhexidine gel and a eugenol-based paste on postoperative alveolar osteitis in patients having third molars extracted: a randomised controlled clinical trial. Br J Oral Maxillofac Surg (2015), http://dx.doi.org/10.1016/j.bjoms.2015.06.022
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Table 1 Pain and wound healing in the three groups. Variable Pain, day 1: Mean (SD) SE 95% CI of mean Pain, day 3: Mean (SD) SE 95% CI of mean Pain, day 7: Mean (SD) SE 95% CI of mean Wound healing, day 1: Mean (SD) SE 95% CI of mean Wound healing, day 7: Mean (SD) SE 95% CI of mean
Control (n=90)
Chlorhexidine (n=90)
Eugenol (n=90)
Total (n=270)
7.53 (0.64) 0.067 7.4 to 7.67
6.4 (0.49) 0.052 6.30 to 6.50
5.42 (0.54) 0.057 5.31 to 5.54
6.45 (1.03) 0.063 6.33 to 6.58
5.41 (0.91) 0.096 5.22 to 5.60
3.33 (0.81) 0.085 3.16 to 3.50
1.62 (0.63) 0.066 1.49 to 1.75
3.46 (1.74) 0.106 3.25 to 3.66
3.14 (1.36) 0.144 2.86 to 3.43
1.73 (0.93) 0.098 1.54 to 1.93
0.39 (0.58) 0.061 0.27 to 0.51
1.76 (1.51) 0.092 1.57 to 1.94
5.5 (0.60) 0.064 5.37 to 5.63
4.39 (0.56) 0.058 4.27 to 4.51
4.47 (0.58) 0.062 4.34 to 4.59
4.79 (0.77) 0.047 4.69 to 4.88
2.51 (0.69) 0.073 2.37 to 2.66
1.69 (0.66) 0.070 1.55 to 1.83
1.32 (0.49) 0.052 1.22 to 1.43
1.84 (0.80) 0.048 1.75 to 1.94
Table 2 Alveolar osteitis. Alveolar osteitis Day 1: Yes No Day 3: Yes No Day 7: Yes No
Control (n=90)
Chlorhexidine (n=90)
Eugenol (n=90)
Total (n=270)
90
90
90
270
90
90
90
270
9 81
2 88
90
11 259
chi square=12.699; df=2; p<0.02
Table 3 A. Mean (SD) pain scores between groups. Day and range
Control (n=90)
Chlorhexidine (n=90)
Eugenol (n=90)
Total (n=270)
Day 1 Range Day 3 Range Day 7 Range
7.53 (0.64) 6-9 5.41 (0.91) 3-7 3.14 (1.36) 2-7
6.40 (0.49) 6-7 3.33 (0.81) 2-7 1.73 (0.93) 0-8
5.42 (0.54) 4-6 1.62 (0.63) 0-3 0.39 (0.58) 0-3
6.45 (1.03) 4-9 3.46 (1.74) 0-7 1.76 (1.51) 0-8
B. Analysis of Variance Day
df
Mean square
F value
p value
1 3 7
2 2 2
100.459 324.011 170.878
319.486 518.202 167.668
<0.001 <0.001 <0.001
Please cite this article in press as: Jesudasan JS, et al. Effectiveness of 0.2% chlorhexidine gel and a eugenol-based paste on postoperative alveolar osteitis in patients having third molars extracted: a randomised controlled clinical trial. Br J Oral Maxillofac Surg (2015), http://dx.doi.org/10.1016/j.bjoms.2015.06.022
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Table 4 A. Number (%) with inflammation. Inflammation Day 1: Yes No Day 3: Yes No Day 7: Yes No
Control (n=90)
Chlorhexidine (n=90)
Eugenol (n=90)
Total (n=270)
90
90
2 88
2 268 (99)
87 3
43 47
2 88
132 (49) 138 (51)
13 77
2 88
0 90
15 (6) 255 (94)
B. Chi square analysis Day
Chi square
df
p value
1 3 7
4.03 160.702 20.753
2 2 2
0.133 <0.001 <0.001
Table 5 A. Within-subjects effects: pain score (sphericity assumed).
Pain score Pain score intervention group Error (pain score)
Type III sum of squares
df
Mean square
F value
p value
3.53.069 65.183 249.081
2 4 534
1526.535 16.296 0.466
3272.702 34.936
<0.001 <0.001
B. Between-subjects effects - pain score: transformed variable – mean. Source
Type III sum of squares
df
Mean square
F value
p value
Intercept Intervention group Error
12242.223 1125.514 273.930
1 2 267
12242.223 562.757 1.026
11932.531 548.521
<0.001 <0.001
The male:female ratio did not differ significantly and was uniformly distributed among the 3 groups. The incidence of alveolar osteitis (4%) was much less than reported elsewhere.3,5–8 Of the 90 patients in each group, 9 from the control group and 2 from the chlorhexidine group developed were affected. The eugenol group had no cases, and eugenol was therefore the better preventative. There were fewer cases of alveolar osteitis in the chlorhexidine group than in the control group, which is consistent with previous reports. This suggests that chlorhexidine reduces rates of alveolar osteitis by 25% to 80% after the extraction of impacted mandibular third molars .8,11,13,14 The active components of the interventions cited in previous studies have possessed antibacterial and analgesic properties, or a topical anaesthetic, or a combination, that have resulted in reduction in the incidence of alveolar osteitis.3,7 Chlorhexidine has been shown to be a good prophylactic for dry socket alveolitis. In a study by Ragno and Szkutnik,15 0.2% chlorhexidine digluconate mouthwash produced a reduction in alveolar osteitis after extraction of impacted third molars from 160 sites (from 29/80 (36%) to 14/80 (17.5%) in a control group). Bloomer4 reported that the incidence of localised osteitis was 8/100 sockets that were immediately packed (with ¼–inch radiographically-detectable filament gauze that contained 9%
eugenol, 36% balsam of Peru, and 55% petroleum jelly) and 26/100 sockets that were not immediately packed. The overall low incidence of alveolar osteitis in our trial that spanned over 1½ years could be attributed to the fact that all patients were apparently healthy. Smokers,16–19 people who misused alcohol, and women on oral contraceptives13,17,20–22 were also excluded. Surgical expertise and strict asepsis could also have contributed. The incidence of infection followed a similar pattern to that of alveolar osteitis, and this was not commonly reported in other papers, there being 13 cases in the control group and 2 in the chlorhexidine group, with none in the eugenol group. Comparison of the postoperative pain scores showed that eugenol significantly reduced postoperative pain. Given the severe pain and subsequent anxiety of patients with alveolar osteitis, pain relief is the primary goal of treatment. Jorkjend and Skoglund compared the effects of 2 periodontal dressings containing eugenol and 1 dressing without eugenol on postoperative pain after gingivectomy, and found that eugenol had a significant effect in the control of postoperative pain.13 Acemannan (an extract of aloe vera) inhibits the inflammatory process and relieves pain by interfering with the arachidonic acid pathway by way of cyclooxygenase. Eugenol can also inhibit the inflammatory process and provide analgesic
Please cite this article in press as: Jesudasan JS, et al. Effectiveness of 0.2% chlorhexidine gel and a eugenol-based paste on postoperative alveolar osteitis in patients having third molars extracted: a randomised controlled clinical trial. Br J Oral Maxillofac Surg (2015), http://dx.doi.org/10.1016/j.bjoms.2015.06.022
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effects by inhibition of the action of prostaglandins, which significantly reduced postoperative pain compared with the other 2 groups. The changes in inflammation among the 3 groups also differed (Table 4). As mentioned before both chlorhexidine and eugenol seem to possess anti-inflammatory properties and this was evident from our study. The significant difference in infection in the eugenol group can be attributed to the fact that low concentrations of eugenol exert anti-inflammatory and local anaesthetic effects on oral tissue.13 Wound healing did not show a significant difference between the two intervention groups but with the control only. Eugenol showed not only superior pain relief and anti-inflammatory properties but also better wound healing compared with the other 2 groups. We conclude that there seems to be a clear advantage to the use of intra-alveolar medication after extraction of lower third molars, since the results from previous studies concerning the placement of intra-alveolar drugs for the prevention of alveolar osteitis are controversial, their use does not seem to be indicated at the present. We know of no published clinical trial similar to ours that has compared the use of a chlorhexidine gel or a eugenol-based paste placed in the alveolus for the prevention of alveolitis after the extraction of impacted third molars. We can therefore compare our study only with other trials of other products and other presentations of chlorhexidine and eugenol. Chlorhexidine perioperatively has consistently been shown to deliver a substantial reduction in alveolar osteitis and can be a useful intra-alveolar medication when used in gel form as we did. Eugenol has long been used as an effective treatment for dry socket. Eugenol proved to be the most effective of the two interventions not only in relation to the incidence of alveolar osteitis but also the presence of pain, infection, inflammation, and wound healing. We suggest the routine use of eugenol paste (Alvogyl) after extraction of a third molar not only as a preventative measure against alveolar osteitis but also to reduce pain, inflammation, and promote wound healing. Ideally, a specific guideline should be developed from the available scientific evidence on the prophylactic management of alveolar osteitis during dental extractions to benefit general practitioners and oral surgeons in providing optimal patient care. Conflict of Interest We have no conflict of interest. Ethics statement/confirmation of patients’ permission The trial was approved by the Institutional Ethics Committee and The Institutional Research Committee. Each patient gave consent to participation in the trial.
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References 1. Crawford YJ. Dry sockets after extraction. Dental Cosmos 1896;38:929–31. 2. Birn H. Etiology and pathogenesis of fibrinolytic alveolitis (dry socket). International Journal of Oral Surgery 1973;2:211–63. 3. Blum IR. Contemporary views on dry socket (alveolar osteitis): a clinical appraisal of standardization, aetiopathogenesis and management: a critical review. Int J Oral Maxillofac Surg 2002;31:309–17. 4. Bloomer CR. Alveolar osteitis prevention by immediate placement of medicated packing. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2000;90:282–4. 5. Torres-Lagares D, Gutierrez-Perez JL, Infante-Cossio P, et al. Randomized, double-blind study on effectiveness of intra-alveolar chlorhexidine gel in reducing the incidence of alveolar osteitis in mandibular third molar surgery. Int J Oral Maxillofac Surg 2006;35:348–51. 6. Lilly GE, Osbon DB, Rael EM, et al. Alveolar osteitis associated with mandibular third molar extractions. J Am Dent Assoc 1974;88:802–6. 7. Alexander RE. Dental extraction wound management: a case against medicating postextraction sockets. J Oral Maxillofac Surg 2000;58:538–51. 8. Berwick JE, Lessin ME. Effects of a chlorhexidine gluconate oral rinse on the incidence of alveolar osteitis in mandibular third molar surgery. J Oral Maxillofac Surg 1990;48:444–9. 9. Larsen PE. The effect of a chlorhexidine rinse on the incidence of alveolar osteitis following the surgical removal of impacted mandibular third molars. J Oral Maxillofac Surg 1991;49:932–7. 10. Hermesch CB, Hilton TJ, Biesbrock AR, et al. Perioperative use of 0.12% chlorhexidinegluconate for the prevention of alveolar osteitis: efficacy and risk factor analysis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1998;85:381–7. 11. Tjernberg A. Influence of oral hygiene measures on the development of alveolitis sicca dolorosa after surgical removal of mandibular third molars. Int J Oral Surg 1979;8:430–4. 12. Aronovich S, Skope LW, Kelly JP, et al. The relationship of glycemic control to dental extractions. J Oral Maxillofac Surg 2010;68: 2955–61. 13. Jorkjend L, Skoglund LA. Effect of non-eugenol- and eugenol containing periodontal dressings on the incidence and severity of pain after periodontal soft tissue surgery. J Clin Periodontol 1990;17: 341–4. 14. Brekke JH, Bresner M, Reitman MJ. Effect of surgical trauma and polylactate cubes and granules on the incidence of alveolar osteitis in mandibular third molar extraction wounds. J Can Dent Assoc 1986;52:315–9. 16. Ragno Jr JR, Szkutnik AJ. Evaluation of 0.12% chlorhexidine rinse in the prevention of alveolar osteitis. Oral Surg Oral Med Oral Pathol 1991;72:524–6. 17. Larsen PE. Alveolar osteitis after surgical removal of impacted mandibular third molars: identification of the patient at risk. Oral Surg Oral Med Oral Pathol 1992;73:393–7. 18. Sweet JB, Butler DP. Predisposing and operative factors: effect on the incidence of localized osteitis in mandibular third-molar surgery. Oral Surg Oral Med Oral Pathol 1978;46:206–15. 19. Butler DP, Sweet JB. Effect of lavage on the incidence of localized osteitis in mandibular third molar extraction sites. Oral Surg Oral Med Oral Pathol 1977;44:14–20. 20. Schow SR. Evaluation of postoperative localized osteitis in mandibular third molar surgery. Oral Surg Oral Med Oral Pathol 1974;38: 352–8. 21. Johnson WS, Blanton EE. An evaluation of 9-aminoacridine/Gelfoam to reduce dry socked formation. Oral Surg Oral Med Oral Pathol 1988;66:167–70. 22. Barclay JK. Metronidazole and dry socket: prophylactic use in mandibular third molar removal complicated by non-acute pericoronitis. N Z Dent J 1987;83:71–5.
Please cite this article in press as: Jesudasan JS, et al. Effectiveness of 0.2% chlorhexidine gel and a eugenol-based paste on postoperative alveolar osteitis in patients having third molars extracted: a randomised controlled clinical trial. Br J Oral Maxillofac Surg (2015), http://dx.doi.org/10.1016/j.bjoms.2015.06.022