|Year : 2014 | Volume
| Issue : 2 | Page : 35-40
Bioadhesive chlorhexidine gel for reduction of alveolar osteitis incidence: Systematic review and meta-analysis of randomized controlled trials
Mahmood Reza Kalantar Motamedi1, Saber Khazaei2
1 Dental Students Research Center, School of Dentistry, Isfahan University of Medical Sciences, Isfahan, Iran
2 Research Department, School of Dentistry, Kermanshah University of Medical Sciences, Kermanshah, Iran
|Date of Web Publication||2-Jun-2014|
Research Department, School of Dentistry, Kermanshah University of Medical Sciences, Kermanshah
Source of Support: None, Conflict of Interest: None
Introduction: Alveolar osteitis (AO) creates severe and self-limiting pain, which needs to be treated with several postoperative visits, leading to increases in patient's morbidity and costs. Hence, the most basic and best treatment could be prevention. The aim of this study was to investigate the efficacy of bioadhesive chlorhexidine (CHX) gel in reducing AO occurrence with published studies. Materials and Methods: Medline/PubMed, Scopus, EBSCO, Ovid and Cochrane central registry for control trial were searched up to 28 February 2014 using "alveolar osteitis" and "chlorhexidine" as key words for systematic review and meta-analysis. Inclusion criteria were prospective and randomized controlled trials (RCTs) published on this topic. From the chosen studies, the eligible articles were reviewed. Data were analyzed using Review Manager 5.2 software. Results: Out of 43 studies, seven eligible trials with 593 participants were selected. Bioadhesive 0.2% CHX gel prevented approximately 72% of AO (Odd ratio (OR) = 0.28, 95% confidence Interval (CI): 0.18-0.44; P < 0.001). Conclusion: Bioadhesive 0.2% CHX gel may be effective as a post-medication to reduce incidence of AO.
Keywords: Alveolar osteitis, chlorhexidine, systematic review
|How to cite this article:|
Motamedi MK, Khazaei S. Bioadhesive chlorhexidine gel for reduction of alveolar osteitis incidence: Systematic review and meta-analysis of randomized controlled trials. Dent Hypotheses 2014;5:35-40
|How to cite this URL:|
Motamedi MK, Khazaei S. Bioadhesive chlorhexidine gel for reduction of alveolar osteitis incidence: Systematic review and meta-analysis of randomized controlled trials. Dent Hypotheses [serial online] 2014 [cited 2020 Sep 29];5:35-40. Available from: http://www.dentalhypotheses.com/text.asp?2014/5/2/35/133420
| Introduction|| |
Alveolar osteitis (AO) known as dry socket and is identified as a severe pain in or around the site of an extracted tooth, intensifying any time between the first and third postoperative days, accompanying with partial or total blood clot loss in the alveolar socket.  AO is a common complication following surgical removal of impacted mandibular third molar (up to 30%) and extraction of any other teeth (up to 70%). ,,,, This is a multifactorial condition and the exact causative agent is not clear; however, fibrinolytic cascade and bacterial factors have been reported as the main ones. ,
AO leads to severe pain, which needs several postoperative visits to be treated, leading to increase in patient's morbidity and costs. Owing to the proposed microbial origin, prevention of AO has focused on systemic and topical antimicrobial therapies.
Chlorhexidine (CHX), povidone iodine, 9-aminoacridine, metronidazole, tetracycline, and clindamycin in both systemic and localized regimens have been utilized as preventatives with varying degrees of success. ,, Of them, the most extensively tested therapy was CHX due to its broad spectrum of activity versus oral aerobes and anaerobes, general tolerability, and absence of resistance development. , On the contrary, a number of authors found it ineffective. ,,
The introduction of bioadhesive CHX gel turned lights on a new line of investigation. ,, The gel could be more effective than mouthwash because when positioned intra-alveolar provides more bioavailability and prolonged release of the active substance and also can act directly on the alveolus. ,,
Several studies regarding local interventions, especially, the use of CHX for prevention of AO have been performed, but no one has focused particularly on bioadhesive CHX gel. ,,, On the other hand, it has been reported that short-term use of CHX mouthwash can cause some adverse effects such as an irritation or a burning sensation in oral mucosa and also discoloration of teeth or mucosa. , It seems that CHX gel due to the local placement within the alveolar socket and a single-dose administration may alleviate such adverse effects.
The aim of present study was to systematically review pervious randomized controlled trials (RCTs) on the efficacy of bioadhesive CHX gel in reducing of AO occurrence.
| Materials and Methods|| |
Electronic searches were performed using "alveolar osteitis" and "chlorhexidine" as key words for title and abstract in medical subject headings (MeSH) word search. References of each article were also reviewed.
This review study has been searched up to 28 February 2014 in Medline/PubMed, Scopus, EBSCO, Ovid and Cochrane central registry for controlled trial by searching mentioned key words. A total of 43 studies were found. PubMed query translation was "dry socket" [MeSH] or "alveolar osteitis" [MeSH], and "chlorhexidine" [MeSH]. The search through Medline and Cochrane central register for control trial listed out 37 and 17 articles, respectively, which all overlapped with the results found in PubMed.
Inclusion criteria were limited to the journal articles in prospective RCTs in English language. Articles were excluded if they did not fulfill one or all of the inclusion criteria, if no control group (e.g. placebo (any material different from CHX gel), rinse, and no intervention) was used, and if the outcome of interest was other than incidence of AO.
The outcome measure was set on incidence of AO.
For data extraction, we designed a check list, regarding AO and CHX gel including author, year, country, sample size, study design, and main outcomes of each study [Table 1]. Two authors [Mahmood Reza Kalantar Motamedi and Saber Khazaei], who were not blinded, performed all searches and review procedures from the beginning to the end, independently. In the case of disagreement between evaluators, it reassessed by discussion and a final consensus was agreed on. [Figure 1] provides information on the number of papers identified through the search strategy. Moreover, cross-references were screened to identify further trials that probably were missed through the search strategy. However, no additional trials were found.
The data were analyzed using review manager software (version 5.2). Inverse-variance weighting was implemented to calculate the random effect summary estimates and to produce a forest plot using the number of participants with events and total number of participants in experimental and control groups of each study.
| Results|| |
Out of initial 43 articles, seven letters to the editor (comments on previous studies), nine reviews, nine studies due to lacking relevance to the subject, and 10 articles because they had evaluated CHX rinse (CHX gel was not tested) were excluded. Among eight remained articles, the full texts were obtained, and they were considered based on compliance with exclusion/inclusion criteria. Finally, seven RCTs ,,,,,, fully met the criteria for detailed analysis. The reasons for excluding the one study was that Rodríguez-Pérez et al., did not used any placebo gel, in fact, they compared two different amounts of CHX gel (1 and 0.2%) without using another control group using some materials different from CHX gel. 
CHX (0.2% concentrations) after surgery prevented 72% of AO (OR = 0.28, 95% confidence interval (CI): 0.18-0.44; P < 0.001) (seven trials, 593 participants) [Figure 2]. Also, the prevalence of dry socket varied from 6.67 to 32.5% in surgically extracted third molars. Out of the selected RCTs, two studies had a split-mouth design and five did not have. Four and two trials were performed in Spain and Iran, respectively, with same study authors [Table 1].
|Figure 2: Forest plot of comparison between CHX gel versus placebo; CHX = Chlorhexidine; M-H = Mantel-Haenszel, 95% CI: 95% confidence interval, df: degree of freedom|
Click here to view
| Discussion|| |
This meta-analysis study was carried out to review and study the efficacy of bioadhesive CHX gel compared with placebo used to reduce the incidence of AO in patients who were candidate for bilateral tooth extractions. Considering this searching strategy, seven articles met the criteria for final evaluation. Based on these studies, a single-dose administration of 0.2% bioadhesive CHX gel reduces the incidence of AO.
Several factors can increase the risk of AO incidence such as tobacco smoking, ,, drinking,  herpes,  level of tooth impaction, , periodontal problems, , poor oral hygiene, ,, surgical site, , preoperative infection, , aging, , female gender, ,, use of local anesthesia with a vasoconstrictor, , ingestion of oral contraceptives, ,, traumatic exodontias, , and lack of experience in the surgeon. ,,, However, the results are controversial  and statistical analyses are mostly inadequate as only a few studies have conducted multivariable analyses. ,,, In a great number of previous studies, such risk factors were included. Therefore, when evaluating the role of CHX in reducing AO incidence, these risk factors can serve as confounding variables. Most of the selected studies included analgesic and antibiotic medications, contraceptive pills, and smoker patients. ,,,, In two included trials with split-mouth design, , the main risk factors comprised smoking and receiving contraceptives; however, due to the use of split-mouth design, the role of confounding variables might be controlled. Haraji et al., , were in this opinion as well, which stated due to the split-mouth design, the variables gender, age, receiving contraceptives, different oral hygiene, and smoking were equal in the treatment and control groups.
It is worth mentioning, Haraji et al., , extracted the teeth with similar surgery difficulty index in both sides of a mouth. This may lead to a further accurate and calibrated split-mouth evaluation. However, of the Haraji's et al., , limitations, although most of confounders were limited in their studies, enrolling only patients who could tolerate postoperative pain without analgesic consumption might be questionable, as the results might not be generalizable to the routine clinical practice.
A proposed responsible factor regarding incidence of AO was microbial agents that may contribute to fibrinolysis and consequent blood clot disintegration.  Several studies have focused on reducing the incidence of AO by decreasing bacterial count in oral cavity.  Therefore, the fact that CHX can reduce the frequency of AO might be due to its broad spectrum of activity versus oral aerobes and anaerobes. ,
A limitation of our study was that only relevant studies in PubMed/Medline, Scopus, EBSCO, Ovid and Cochrane library were searched. The authors suggest for future surveys to utilize split-mouth design with a more control on included AO risk factors.
In conclusion, bioadhesive CHX gel can reduce incidence of AO.
| References|| |
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.
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 Surg1990;48:444-8.
Larsen PE. Alveolar osteitis after surgical removal of impacted mandibular third molars: Identification of the patient at risk. Oral Surg Oral Med Oral Pathol1992;73:393-7.
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.
Ragno Jr JR, Szkutnik AJ. Evaluation of 0.12% chlorhexidine rinse on the prevention of alveolar osteitis. Oral Surg Oral Med Oral Pathol 1991;72:524-6.
Ritzau M, Hillerup S, Branebjerg P, Ersbol B. Does metronidazole prevent alveolitis sicca dolorosa? A double-blind, placebo-controlled clinical study. Int J Oral Maxillofac Surg 1992;21:299-302.
Caso A, Hung LK, Beirne OR. Prevention of alveolar osteitis with chlorhexidine: A meta-analytic review. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2005;99:155-9.
Sweet JB, Macynski AA. Effect of antimicrobial mouth rinses on the incidence of localized alveolitis and infection following mandibular third molar oral surgery. Oral Surg Oral Med Oral Pathol 1985;59:24-6.
Briner W, Grossman E, Buckner R, Rebitski G, Sox T, Ebert M. Assessment of susceptibility of plaque bacteria to chlorhexidine after six months' oral use. J Periodontal Res 1986;21:53-9.
Lang N, Brecx MC. Chlorhexidine digluconate-an agent for chemical plaque control and prevention of gingival inflammation. J Periodontal Res 1986;21:74-89.
Mínguez-Serra MP, Salort-Llorca C, Silvestre-Donat FJ. Chlorhexidine in the prevention of dry socket: Effectiveness of different dosage forms and regimens. Med Oral Patol Oral Cir Bucal 2009;14:e445-9.
Yengopal V, Mickenautsch S. Chlorhexidine for the prevention of alveolar osteitis. Int J Oral Maxillofac Surg 2012;41:1253-64.
Hita-Iglesias P, Torres-Lagares D, Flores-Ruiz R, Magallanes-Abad N, Basallote-Gonzalez M, Gutierrez-Perez JL. Effectiveness of chlorhexidine gel versus chlorhexidine rinse in reducing alveolar osteitis in mandibular third molar surgery. J Oral Maxillofac Surg 2008;66:441-5.
Torres-Lagares D, Gutierrez-Perez J, Infante-Cossio P, Garcia-Calderon M, Romero-Ruiz M, Serrera-Figallo M. 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.
Torres-Lagares D, Gutierrez-Perez JL, Hita-Iglesias P, Magallanes-Abad N, Flores-Ruiz R, Basallote-Garcia M, Gonzalez-Martin M. Randomized, double-blind study of effectiveness of intra-alveolar application of chlorhexidine gel in reducing incidence of alveolar osteitis and bleeding complications in mandibular third molar surgery in patients with bleeding disorders. J Oral Maxillofac Surg 2010;68:1322-6.
Torres-Lagares D, Infante-Cossio P, Gutierrez-Perez JL, Romero-Ruiz MM, Garcia-Calderon M, Serrera-Figallo MA. Intra-alveolar chlorhexidine gel for the prevention of dry socket in mandibular third molar surgery. A pilot study. Med Oral Patol Oral Cir Bucal 2006;179:84.
Daly B, Sharif MO, Newton T, Jones K, Worthington HV. Local interventions for the management of alveolar osteitis (dry socket). Cochrane Database Syst Rev 2012;12:CD006968.
Flötra L, Gjermo P, Rölla G, Waerhaug J. Side effects of chlorhexidine mouth washes. Scand J Dent Res 1971;79:119-25.
Gürgan CA, Zaim E, Bakirsoy I, Soykan E. Short-term side effects of 0.2% alcohol-free chlorhexidine mouthrinse used as an adjunct to non-surgical periodontal treatment: A double-blind clinical study. J Periodontol 2006;77:370-84.
Haraji A, Rakhshan V. Single-dose intra-alveolar chlorhexidine gel application, easier surgeries, and younger ages are associated with reduced dry socket risk. J Oral Maxillofac Surg 2014;72:259-65.
Haraji A, Rakhshan V, Khamverdi N, Alishahi HK. Effects of intra-alveolar placement of 0.2% chlorhexidine bioadhesive gel on dry socket incidence and postsurgical pain: A double-blind split-mouth randomized controlled clinical trial. J Orafac Pain 2013;27:256-62.
Babar A, Ibrahim MW, Baig NJ, Shah I, Amin E. Effcacy of intra-alveolar chlorhexidine gel in reducing frequency of alveolar osteitis in mandibular third molar surgery. J Coll Physicians Surg Pak 2012;22:91-4.
Rodríguez-Pérez M, Bravo-Pérez M, Sánchez-López JD, Muñoz-Soto E, Romero-Olid MN, Baca-García P. Effectiveness of 1% versus 0.2% chlorhexidine gels in reducing alveolar osteitis from mandibular third molar surgery: A randomized, double-blind clinical trial. Med Oral Patol Oral Cir Bucal 2013;18:e693-700.
Abu Younis MH, Abu Hantash RO. Dry socket: Frequency, clinical picture, and risk factors in a palestinian dental teaching center. Open Dent J 2011;5:7-12.
Kolokythas A, Olech E, Miloro M. Alveolar osteitis: A comprehensive review of concepts and controversies. Int J Dent 2010;2010:249073.
Halabí D, Escobar J, Muñoz C, Uribe S. Logistic regression analysis of risk factors for the development of alveolar osteitis. J Oral Maxillofac Surg 2012;70:1040-4.
Parthasarathi K, Smith A, Chandu A. Factors affecting incidence of dry socket: A prospective community-based study. J Oral Maxillofac Surg 2011;69:1880-4.
Cardoso CL, Rodrigues MT, Ferreira Júnior O, Garlet GP, de Carvalho PS. Clinical concepts of dry socket. J Oral Maxillofac Surg 2010;68:1922-32.
Baqain ZH, Karaky AA, Sawair F, Khaisat A, Duaibis R, Rajab LD. Frequency estimates and risk factors for postoperative morbidity after third molar removal: A prospective cohort study. J Oral Maxillofac Surg 2008;66:2276-83.
Oginni FO, Fatusi OA, Alagbe AO. A clinical evaluation of dry socket in a Nigerian teaching hospital. J Oral Maxillofac Surg 2003;61:871-6.
al-Khateeb TL, El-Marsafi AI, Butler NP. The relationship between the indications for the surgical removal of impacted third molars and the incidence of alveolar osteitis. J Oral Maxillofac Surg 1991;49:141-5.
Benediktsdóttir IS, Wenzel A, Petersen JK, Hintze H. Mandibular third molar removal: Risk indicators for extended operation time, postoperative pain, and complications. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2004;97:438-46.
Meechan J, Venchard G, Rogers S, Hobson R, Prior I, Tavares C, et al.
Local anaesthesia and dry socket. A clinical investigation of single extractions in male patients. Int J Oral Maxillofac Surg 1987;16:279-84.
Eshghpour M, Rezaei NM, Nejat A. Effect of menstrual cycle on frequency of alveolar osteitis in women undergoing surgical removal of mandibular third molar: A single-blind randomized clinical trial. J Oral Maxillofac Surg 2013;71:1484-9.
Chuang S-K, Perrott DH, Susarla SM, Dodson TB. Age as a risk factor for third molar surgery complications. J Oral Maxillofac Surg 2007;65:1685-92.
Hermesch CB, Hilton TJ, Biesbrock AR, Baker RA, Cain-Hamlin J, McClanahan SF, et al
. Perioperative use of 0.12% chlorhexidine gluconate for the prevention of alveolar osteitis: Efficacy and risk factor analysis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1998;85:381-7.
[Figure 1], [Figure 2]