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Effect of eugenol in the management of alveolar osteitis: A systematic review
Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology 26 (2014) 101–107
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Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology journal homepage: www.elsevier.com/locate/jomsmp
Oral and Maxillofacial Surgery/Review article
Effect of eugenol in the management of alveolar osteitis: A systematic review James Solomon Jesudasan ∗ , Ashok K. Ramadorai, P.U. Abdul Wahab Department Oral and Maxillofacial Surgery, Saveetha Dental College, 162 Ponamallee High Road, Velapanchavadi, Chennai 600077, India
a r t i c l e
i n f o
Article history: Received 12 February 2013 Accepted 22 May 2013 Available online 18 July 2013 Keywords: Alveolar osteitis Alveolar periostitis Alveolitis sicca dolorosa Dry socket
a b s t r a c t Purpose: One of the most common postoperative complications following the extraction of permanent teeth is a condition known as dry socket or alveolar osteitis (AO). The purpose of this review was to answer the question “Does eugenol have any effect in the management of AO?” Methods: Search: In July 2012 search for relevant trials in The Cochrane Library, MEDLINE and PUBMED (MESH) was done. Selection criteria: Only randomised control trials that used eugenol in management of AO were included in the review. And only human studies of English language were included. Results: In all the four trials a total of 219 patients out of which 86 patients were administered eugenol for the management of alveolar osteitis. Eugenol was found to be more effective than curettage and irrigation and equal to thermosetting gel and Salicept. Eugenol was found to be less effective than low level laser, GECB and Dextranomer granules. Only RCTs were included and all other articles were excluded from the review. © 2013 Asian AOMS, ASOMP, JSOP, JSOMS, JSOM, and JAMI. Published by Elsevier Ltd. All rights reserved.夽
Contents 1. 2.
3.
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5. 6. 7. 8.
Background . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Summary of various treatment options . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.1. Non pharmacological methods [21] . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.2. Pharmacological interventions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.3. Based on the first dictum of medicine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Structured question . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.1. Pico analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.2. Types of outcome measures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Materials and methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.1. Sources used . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.2. Search strategy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.3. Inclusion criteria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.4. Exclusion criteria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.5. Search flow chart . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.6. Search results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.1. General information of included studies (Tables 2–11) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Limitation of the review . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
102 102 102 102 102 102 102 103 103 103 103 103 103 103 103 103 103 103 106 106
夽 AsianAOMS: Asian Association of Oral and Maxillofacial Surgeons; ASOMP: Asian Society of Oral and Maxillofacial Pathology; JSOP: Japanese Society of Oral Pathology; JSOMS: Japanese Society of Oral and Maxillofacial Surgeons; JSOM: Japanese Society of Oral Medicine; JAMI: Japanese Academy of Maxillofacial Implants. ∗ Corresponding author. Tel.: +91 4426801583; mobile: +91 9940482260. E-mail addresses: [email protected], [email protected] (J.S. Jesudasan). 2212-5558/$ – see front matter © 2013 Asian AOMS, ASOMP, JSOP, JSOMS, JSOM, and JAMI. Published by Elsevier Ltd. All rights reserved.夽 http://dx.doi.org/10.1016/j.ajoms.2013.05.014
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9.
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Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9.1. Implications for practice . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9.2. Implications for research . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1. Background Dry socket was first described as a complication of disintegration of the intra-alveolar blood clot, with an onset 2–4 days after extraction. According to Fazakerlev and Field [1], the alveolus empties, the osseous surroundings are denuded and covered by a yellow-grey necrotic tissue layer, and the surrounding mucosa usually becomes erythematous. It is clinically characterised by a putrid odour and intense pain that radiates to the ear and neck [2]. Pain is considered the most important symptom of dry socket. It can vary in frequency and intensity, and other symptoms, such as headache, insomnia, and dizziness, can be present. Calhoun [3] also reported trismus as a frequent symptom that develops 10–40 days after extraction, if the infection does not spread. Regional lymphadenopathy can be present on the affected side, and fever is infrequent. Dry socket is commonly observed in patients 40–45 years old [4,5]. Published data have reported an incidence of 1–4% after teeth extraction, with an incidence 10 times greater for lower teeth than for upper teeth [6] and reaching 45% for mandibular third molars [7,8]. Recently, investigators have suggested the following definition for dry socket: postoperative pain surrounding the alveolus that increases in severity for some period from 1 to 3 days after extraction, followed by partial or total clot loss in the interior of the alveolus, with or without halitosis [9,10]. Numerous methods and techniques are proposed throughout the existing literature to assist with prevention of alveolar osteitis (AO). Systemic antibiotics reported to be effective in the prevention of AO include penicillins, clindamycin, erythromycin, and metronidazole [11,12]. A great number of studies have been performed in order to test the effectiveness of topical medicaments in preventing AO. Several studies have reported that the pre- and perioperative use of 0.12% chlorhexidine [13–15] decreases the frequency of AO after mandibular third molar removal. Lagares et al. used chlorhexidine gel on the reduction of the incidence of impacted third molar post-extraction dry socket alveolitis [16]. Early literature reported that the topical use of para-hydroxybenzoic acid (PHBA) [17,18] an antifibrinolytic agent in extraction wounds, decreased the incidence of AO. Some authors have suggested copious intraoperative lavage to reduce the incidence of AO. Butler and Sweet [8,19] reported significant reduction in AO when 175 ml lavage was used as compared to 25 ml lavage. Bloomer et al. suggest that placement of medicated dry socket packing immediately after lower third molar extraction decreases the alveolar osteitis rate [20].
106 106 106 107
• Extractions should be performed with minimum amount of trauma and maximum amount of care. • Wherever possible preoperative oral hygiene measures to reduce plaque levels to a minimum should be instituted [23]. • Encourage the patient (again) to stop or limit smoking in the immediate postoperative period. • Advise patient to avoid vigorous mouth rinsing for the first 24 h post extraction and to use gentle toothbrushing in the immediate postoperative period. • For patients taking oral contraceptives extractions should ideally be performed during days 23 through 28 of the menstrual cycle [19]. • Comprehensive pre- and postoperative verbal instructions should be supplemented with written advice to ensure maximum compliance. 2.2. Pharmacological interventions • • • • • •
Antibacterial agents. Antiseptic agents and lavage. Antifibrinolytic agents. Steroid anti-inflammatory agents. Obtundent dressings. Clot support agents.
2.3. Based on the first dictum of medicine As stated by Hippocrates (421 BC): ‘At first do no harm’, it seems prudent to limit the pharmacological preventive interventions to measures which are supported by sufficient evidence to be effective, and equally, show a minimum of side effects. Some authors have promoted the use of eugenol containing dressing to prevent development of AO [20,24–27]. Despite many years of research, little progress has been made in addressing this commonly encountered and unpleasant postoperative condition in patients. Why it is important to do this review? Although a variety of treatment methods have been available for alveolar osteitis, there appears to be a paucity of large randomised studies comparing the treatments for alveolar osteitis. There is therefore little research which accurately compares the different interventions with each other and no systematic review has previously been done in this area.
3. Structured question 2. Summary of various treatment options A variety of treatment techniques have been described in the literature [17].
• Does eugenol have any effect in the management of alveolar osteitis (AO)? 3.1. Pico analysis
2.1. Non pharmacological methods [21] • Use of good quality current preoperative radiographs. • Careful planning of the surgery. • Use of good surgical principles [22].
• Population—patients with alveolar osteitis or at risk of developing AO. • Intervention—eugenol. • Control—various management options of AO.
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• Outcome—post operative pain, infection, wound healing, exposed bone, halitosis, unpleasant taste, redness around the socket and debris. 3.2. Types of outcome measures Primary outcome measure was Preoperative and Postoperative pain. Secondary outcomes included infection, wound healing, exposed bone, halitosis, unpleasant taste, redness around the socket and debris but these outcomes varied according to different studies. 4. Materials and methods 4.1. Sources used In July 2012 search for relevant trials in The Cochrane Library, MEDLINE and PUBMED(MESH) was done. Fig. 1. Search strategy: self-explanatory.
4.2. Search strategy Search strategy was developed in accordance with the guidelines outlined in the Cochrane handbook for systematic reviews. Search was done in Cochrane library (1995–July 2012), PUBMED (till 2012) and MEDLINE. The search was widened to include the internet and hand searched reference lists of identified articles. No language restrictions were imposed on the search. To maximise the identification of relevant articles we used the key phrase ‘alveolar osteitis’ and all the other possible related terms to alveolar osteitis and in second search the keywords ‘alveolar osteitis’ and all the other possible related terms to the management of management of alveolar osteitis were searched. All the search terms were included in the appendix given later. The flow chart that follows shows the search strategy of obtained four articles which met the inclusion criteria.
Table 1 Variables of interest. S. no.
Variables of interest
1 2 3
Pre and postoperative pain Other outcomes/method of evaluation Risk of bias
four randomised control trials that were included in this study as per inclusion criteria (Table 1). 5. Results Only four randomised control trials met the inclusion criteria of this review.
4.3. Inclusion criteria
5.1. General information of included studies (Tables 2–11)
Only randomised control trials that used eugenol in management of alveolar osteitis were included in the review. Both males and females and patients of all age who were affected by alveolar osteitis were considered in this study and only human studies of English language were included.
Graphs to show the comparison between eugenol and various other management modalities with regard to postoperative pain as given in the four studies (Figs. 2–5).
4.4. Exclusion criteria The following studies were excluded: • Case reports/case series/cohorts/clinical trials/animal studies, etc. • Studies not in English. • Studies not meeting the inclusion criteria. 4.5. Search flow chart Flow chart shows search strategy (Fig. 1). 4.6. Search results Review of titles and abstracts identified from the searches were done. If it was clear that the study did not refer to randomised control trial then it was excluded. If it was unclear then the full text was obtained and the list of excluded studies were mentioned and reason for exclusion were mentioned. An independent literature search carried out by two of the investigating author’s revealed only
6. Discussion This systematic review examines from 4 RCTs the effect of eugenol in the management of AO. In all of the selected trials a total of 86 patients out of 219 patients used eugenol in the management of AO. Eugenol was compared with other material like Salicept patch, saline irrigation and curettage, thermosetting gel, lasers, GECB and dextranomer granules. According to Kaya et al. [24]. The baseline clinical examinations revealed severe pain in all patients (n = 104; 100%). Other signs and symptoms included halitosis (n = 78, 75%), debris (n = 62, 60%), an empty socket (n = 60, 58%), redness around the socket (n = 50, 48.1%), exposed bone (n = 50, 48.1%), and an unpleasant taste in the mouth (n = 29, 28%). The differences in the changes in the clinical signs and symptoms between the control group and all three treatment groups were statistically significant (P = 0.05) on the third day after treatment. LLLT group showed better results than the other three groups. Alvogyl (eugenol) group was better than irrigation and curettage but no statistical difference was seen between it and the Salicept group. The decrease in pain was significantly greater for the LLLT group than for the alvogyl, Salicept, and control groups. According to Burgoyne et al. [25], the mean pretreatment pain score was 6.72 on a scale ranging from 1 to 10 for the eugenol
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Table 2 Characteristics of included study of Kaya et al. [24]. Methods
Single centre (Department of Oral and Maxillofacial Surgery, Atatürk University)
Participants Interventions
104 Patients with complaint of alveolar osteitis from January 2008 to July 2009 The patients were randomly assigned to 4 groups of 26 patients each Group 1 (control group; 15 women and 11 men), curettage and irrigation alone Group 2 (12 women and 14 men), curettage and irrigation followed by alvogyl applied directly to the socket Group 3 (15 women and 11 men), curettage and irrigation followed by Salicept applied directly to the socket Group 4 (11 women and 14 men), curettage and irrigation followed by LLLT irradiation (808 nm, 100-mW continuous mode gallium aluminium arsenide diode laser Relative decrease in signs and symptoms Preoperatively: Group 1: n = 4, Group 2: n = 4.23, Group 3: n = 4.62, and Group 4: n = 4.69 Postoperatively: Group 1: n = 1.62, Group 2: n = 0.62, Group 3: n = 0.36, and Group 4: n = 0.08 No statistical difference in the management of AO was seen between Groups 2 and 3. However, it was significantly better in Group 4 than the other three groups
Outcomes
Results
Table 3 Risk of bias (Kaya et al. [24]). Item
Author’s judgement
Description
Adequate sequence generation Allocation concealment Blinding all outcomes
Yes Unclear No
Incomplete outcome data addressed? All outcomes
No
Randomisation done Insufficient information to permit judgement Participants and clinicians were not blinded–intervention Administration vs. observation only. Not clear whether outcome assessors were blinded All the 104 patients were initially randomised. And the outcomes were measured. No patients were missing during the follow up
Table 4 Characteristics of included study of Burgoyne et al. [25]. Methods
Single centre (Department of Oral and Maxillofacial Surgery, School of Dentistry, Virginia Commonwealth University, Richmond, VA)
Participants Interventions
35 Patients with alveolar osteitis Group A: There were 5 males and 15 females (Control) Group B: There were 8 males and 7 females (treatment) Visual analogue scale for pain Preoperative mean value. Group A: 6.72 and Group B: 6.37 Postoperative mean value. Group A: 3.2 ± 0.62 and Group B: 4.83 ± 0.43 The efficacy of the two treatments was not significantly different
Outcomes
Results
Table 5 Risk of bias (Burgoyne et al. [25]). Item
Author’s judgement
Description
Adequate sequence generation Allocation concealment Blinding all outcomes
No Unclear No
Incomplete outcome data addressed? All outcomes
No
Not mentioned clearly Insufficient information to permit judgement Participants and clinicians were not. Not clear whether outcome assessors were blinded All the 35 patients were initially randomised. And the outcomes were measured. No patients were missing during the follow up
Table 6 Characteristics of included study of Haghighat et al. [27]. Methods
Single centre (Maxillofacial Surgery Department Of Isfahan University Of Medical Sciences)
Participants Interventions
30 Patients diagnosed with dry socket syndrome after impacted lower third molar extraction were selected Group 1: 15 patients (11 males and 4 females) undergone treatment with ZOE Group 2: 15 patients (7males and 8 females) were treated with pastille GECB Duration of pain after treatment. Group 1: Pain persisted for 45.53 ± 33.34 min. Group 2: 19.87 ± 21.80 min GECB showed more significant efficacy in reducing complications than ZOE
Outcomes Results Table 7 Risk of bias (Haghighat et al. [27]). Item
Author’s judgement
Description
Adequate sequence generation Allocation concealment Blinding all outcomes
No Unclear No
Incomplete outcome data addressed? All outcomes
No
Not mentioned clearly Insufficient information to permit judgement Participants and clinicians were not blinded. Not clear whether outcome assessors were blinded All the 30 patients were initially randomised. And the outcomes were measured. No patients were missing during the follow up
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Table 8 Characteristics of included study of Majati et al. [26]. Methods
Single centre (K.L.E.V.K. Institute of Dental Sciences, Belgaum, India)
Participants Interventions
A sample of 50 patients was studied Group A: Received zinc oxide eugenol dressing Group B: Received dextranomer dressing Control of pain and promotion of wound healing Group A: pain relief with statistically significant t value. 6.5248 Group B: pain relief with statistically significant t value. 4.8980 Statistically significant result was in favour of dextranomer dressing
Outcomes
Results
Table 9 Risk of bias (Majati et al. [26]). Item
Author’s judgement
Description
Adequate sequence generation Allocation concealment Blinding all outcomes
No Unclear No
Incomplete outcome data addressed? All outcomes
No
Not mentioned clearly Insufficient information to permit judgement Participants and clinicians were not. Not clear whether outcome assessors were blinded All the 50 patients were initially randomised. And the outcomes were measured. No patients were missing during the follow up
Fig. 4. Study 3. Haghighat et al. [27]. X axis, time in minutes taken to reduce pain and Y axis, different management modalities used by the author. GECB and eugenol.
Fig. 2. Study 1: Kaya et al. [24]. X axis, number of patients; Y axis, different management modalities used by the author; C&I, curettage and irrigation; eugenol, Alvogyl; Salicept, Salicept patch; and LLLT, low level laser treatment.
Fig. 5. Study 4: Majati et al. [26]. X axis, number of days taken for pain relief and Y axis, different management modalities used by the author. Dextranomer granules and ZOE. Table 10b Level of evidence according to the United Kingdom National Health Service. Fig. 3. Study 2: Burgoyne et al. [25]. X axis, pain score (VAS 1–10) and Y axis, different management modalities used by the author. Thermosetting gel and eugenol.
Table 10a Level of evidence according to the United States Department of Health and Human Services. S. no.
Author
Year
Design
Level of evidence
1 2 3 4
Kaya et al. [24] Burgoyne et al. [25] Haghighat et al. [27] Majati et al. [26]
2011 2010 2012 2010
RCT RCT RCT RCT
1 1 1 1
S. no.
Author
Year
Design
Level of evidence
1 2 3 4
Kaya et al. [24] Burgoyne et al. [25] Haghighat et al. [27] Majati et al. [26]
2011 2010 2012 2010
RCT RCT RCT RCT
Level A Level A Level A Level A
group and 6.37 for the prilocaine-lidocaine group with no statistical difference. In the immediate post-treatment period (0–15 min) the pain levels were significantly reduced in both groups. However, the thermosetting gel produced a significantly greater reduction in pain (mean, 3.23; SE, 0.62) than the eugenol (mean, 4.83; SE, 0.43). Over the next 48 h, the pain level was nominally less with the thermosetting gel, but this difference was not statistically significant.
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Table 11 Summation table for individual parameters of all four studies. Study 1: Kaya et al. [24]
Signs, symptoms Pre op pain Post op pain Unpleasant taste Halitosis Empty socket Exposed bone Redness Debris Healing
Study 2: Burgoyne et al. [25]
Study 3: Haghighat et al. [27]
Study 4: Majati et al. [26]
Eugenol
Curettage and irrigation
Salicept
LLLT
Eugenol
Thermosetting gel
Eugenol
GECB
Eugenol
4.3 26n 6n 0n 2n 2n 1n 1n 2n *
4 26n 23n 2n 3n 0n 1n 12n 2n *
4.62 26n 3n 0n 2n 1n 0n 0n 0n *
4.69 26n 1n 0n 0n 0n 0n 0n 1n *
* 6.72 VAS 4.83 VAS * * * * * * *
* 6.37 VAS 3.23 VAS * * * * * * *
* 8.33 VAS 45.53 min * * * * * * 45.53 min
* 8.27 VAS 19.87 min * * * * * * 9.87 min
* * 4.2 days * * * * * * 5.3 days
VAS, visual analogue scale (1–10); min, time in minutes; days, duration in days; n, number of patients; *, no data available relating to this.
According to them although the efficacy of the two treatments was not significantly different, the nominal superiority and ease of using the thermosetting gel warranted further investigation. Majati et al. [26] said that statistically significant results with respect to pain control and initial healing were obtained in favour of dextranomer dressing. They also said that mean period for complete pain relief was 4.2 days with zinc oxide eugenol dressing as against 2.8 days with dextranomer dressing and Mean period for initial healing was 5.3 days in zinc oxide dressing as against 3.5 days in dextranomer dressing. They said that this could be attributed to its absorbent action which removes local kinins, exudates, bacteria and toxins which are responsible for causing pain by irritating the free nerve endings. According to Haghighat et al. [27], pain persisted for 45.53 ± 33.34 min in patients treated with ZOE and 19.87 ± 21.80 min in those treated with GECB. They also said that patients in the ZOE group reported more painkiller intake within 20 days. They concluded that because of GECB pastille convenience and its one session use with less chair time, compared to ZOE, it can be an effective and reliable alternative for traditional ZOE method. 7. Summary Does eugenol have an effect in the management of alveolar osteitis? According to the review conducted with the four RCT’s there is no doubt that eugenol has an effect in the management of alveolar osteitis. According to Kaya et al. [24], Alvogyl (eugenol) group was better than irrigation and curettage but no difference was seen between it and the Salicept group. They concluded that in their study LLLT was the best option among the management options they compared for AO. Burgoyne et al. [25] said that the pain levels were significantly reduced in both groups that they compared (both the eugenol and the thermosetting gel groups). According to the study by Majati et al. [26] they said that significant results with respect to pain control and initial healing were obtained in favour of dextranomer dressing over eugenol but suggested further larger studies to obtain more conclusive results. Haghighat et al. [27] concluded that because of GECB pastille convenience and its one session use with less chair time, compared to ZOE, it can be an effective and reliable alternative for traditional ZOE method. In all the four trials a total of 219 patients out of which 86 patients were administered eugenol for the management of AO. Eugenol was found to be more effective than curettage and irrigation and equal to thermosetting gel and Salicept. Eugenol was
found to be less effective than low level laser, GECB and dextranomer granules. 8. Limitation of the review In spite of a large number of studies identified by this review, the quality of follow-up data and assessment variables for the effect of eugenol in the management of AO were limited. The majority of the studies do not provide a statistical analysis of the variables that were used. Furthermore, there is inconsistency in literature regarding a definitive management for AO. The few studies that compared eugenol with other modalities don’t provide the necessary data to draw stronger conclusions. Of the studies included in this review, complications were rarely addressed and therefore the lack of unmatched studies in this regard may lead to a bias. Furthermore the small sample of qualifying articles may mask the presence of significant results. The studies identified were generally small with an average of 30 cases per study. The numbers of cases eligible for analysis were further restricted by the way in which data had been published. We also acknowledge the potential presence of publication bias within this review. Owing to the small numbers of studies included, an assessment could not be performed in greater detail. No unpublished data was included. 9. Conclusion 9.1. Implications for practice Although good quality research exists on the efficacy of different treatment modalities of AO only four suitable Randomised control trial were obtained following a literature search by two different investigators regarding the effect of eugenol in the management of AO. All the studies showed post-operative decrease in pain and complications with the use of eugenol. Hence we conclude that eugenol is a viable and safe option for the management of alveolar osteitis but not necessarily the best option when compared to other options available. 9.2. Implications for research a) There is a great need for well-designed randomised studies to evaluate the use of eugenol in AO. b) Such studies should preferably address all the following outcomes: pre and postoperative pain, rate of infection, wound healing, bone exposure, halitosis and complications. c) Standardised outcome measures would make studies easier to compare.
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d) The statistical power of the study will need careful consideration and problems with accuracy of sufficient numbers of participants will need to be addressed. A multicentre approach may need to be adopted if accuracy rates are likely to be low.
References [1] Fazakerlev M, Field EA. Dry socket: a painful post-extraction complication (a review). Dent Update 1991;18:31–4. [2] Swanson AE. A double-blind study on the effectiveness of tetracycline in reducing the incidence of fibrinolytic alveolitis. J Oral Maxillofac Surg 1989;47:165–7. [3] Calhoun NR. Dry socket and other postoperative complications. Dent Clin North Am 1971;15:337–48. [4] Rud J. Removal of impacted lower third molars with acute pericoronitis and necrotizing gingivitis. Br J Oral Surg 1970;7:153–60. [5] Rood JP, Danford M. Metronidazole in the treatment of dry socket. Int J Oral Surg 1981;10:345–7. [6] Alling III CC, Helfrick JF, Alling RD. Impacted teeth. Philadelphia: WB Saunders; 1993. [7] Trieger N, Schlagel GD. Preventing dry socket: a simple procedure that works. J Am Dent Assoc 1991;122:67–8. [8] 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 Oral Radiol Endod 1977;44:14–20. [9] Crawford JY. Dry socket. Dental Cosmos 1896;38:929–31. [10] Torres-Lagares D, Serrera-Figallo MA, Romero-Ruíz MM, Infante-Cossío P, García-Calderón M, Gutiérrez-Pérez JL. Update on dry socket: a review of the literature. Med Oral Patol Oral Cir Bucal 2005;10:77–81. [11] Ingham HR, Hood FJ, Bradnum P, Tharagonnet D, Selkon JB. Metronidazole compared with penicillin in the treatment of acute dental infections. Br J Oral Surg 1977;14:264–9. [12] Chapnick P, Diamond LH. A review of dry socket: a doubleblind study on the effectiveness of clindamycin in reducing the incidence of dry socket. J Can Dent Assoc 1992;58:43–52. [13] 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.
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[14] 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;48:444–8. [15] Larsen PE. Use of chlorhexidine to prevent alveolar osteitis. J Oral Maxillofac Surg 1990;48:1244–5. [16] Torres-Lagares D, Gutierrez-Perez JL, Infante-Cossio P, Garcia-Calderon M, Romero-Ruiz MM, Serrera-Figallo MA. 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. [17] Birn HH. Etiology and pathogenesis of fibrinolytic alveolitis (‘dry socket’). Int J Oral Surg 1973;2:211–63. [18] Schatz JP, Fiore-Donno G, Henning G. Fibrinolytic alveolitis and its prevention. Int J Oral Maxillofac Surg 1987;16(1):75–183. [19] 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. [20] Bloomer CR. Alveolar osteitis prevention by immediate placement of medicated packing. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2000;90: 282–4. [21] 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. [22] Triger N, Schlagel GD. Preventing dry socket: a simple procedure that works. J Am Dent Assoc 1991;2:67–8. [23] Tjernberg A. Influence of oral hygiene measures on the development of alveolitis sicca dolorosa after surgical removal of mandibular third molars. Int J Oral Maxillofac Surg 1979;8:430–4. [24] Kaya GS¸, Yapici G, Savas¸ Z, Güngörmüs¸ M. Comparison of alvogyl, SaliCept patch, and low-level laser therapy in the management of alveolar osteitis. J Oral Maxillofac Surg 2011;69:1571–7. [25] Burgoyne CC, Giglio JA, Reese SE, Sima AP, Laskin DM. The efficacy of a topical anesthetic gel in the relief of pain associated with localized alveolar osteitis. J Oral Maxillofac Surg 2010;68:144–8. [26] Majati SS, Kulkarni D, Kotrashetti SM, Lingaraj JB, Janardhan S. Study of dextranomer granules in treatment of alveolar osteitis: a prospective study of 50 cases. J Int Oral Health 2010;2:99–103. [27] Haghighat A, Bahri Najafi R, Bazvand M, Badrian H, Khalighinejad N, Goroohi H. The effectiveness of GECB pastille in reducing complications of dry socket syndrome. Int J Dent 2012;2012:587461, http://dx.doi.org/10.1155/2012/587461.
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Oral and Maxillofacial Surgery/Review article
Effect of eugenol in the management of alveolar osteitis: A systematic review James Solomon Jesudasan ∗ , Ashok K. Ramadorai, P.U. Abdul Wahab Department Oral and Maxillofacial Surgery, Saveetha Dental College, 162 Ponamallee High Road, Velapanchavadi, Chennai 600077, India
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Article history: Received 12 February 2013 Accepted 22 May 2013 Available online 18 July 2013 Keywords: Alveolar osteitis Alveolar periostitis Alveolitis sicca dolorosa Dry socket
a b s t r a c t Purpose: One of the most common postoperative complications following the extraction of permanent teeth is a condition known as dry socket or alveolar osteitis (AO). The purpose of this review was to answer the question “Does eugenol have any effect in the management of AO?” Methods: Search: In July 2012 search for relevant trials in The Cochrane Library, MEDLINE and PUBMED (MESH) was done. Selection criteria: Only randomised control trials that used eugenol in management of AO were included in the review. And only human studies of English language were included. Results: In all the four trials a total of 219 patients out of which 86 patients were administered eugenol for the management of alveolar osteitis. Eugenol was found to be more effective than curettage and irrigation and equal to thermosetting gel and Salicept. Eugenol was found to be less effective than low level laser, GECB and Dextranomer granules. Only RCTs were included and all other articles were excluded from the review. © 2013 Asian AOMS, ASOMP, JSOP, JSOMS, JSOM, and JAMI. Published by Elsevier Ltd. All rights reserved.夽
Contents 1. 2.
3.
4.
5. 6. 7. 8.
Background . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Summary of various treatment options . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.1. Non pharmacological methods [21] . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.2. Pharmacological interventions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.3. Based on the first dictum of medicine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Structured question . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.1. Pico analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.2. Types of outcome measures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Materials and methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.1. Sources used . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.2. Search strategy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.3. Inclusion criteria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.4. Exclusion criteria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.5. Search flow chart . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.6. Search results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.1. General information of included studies (Tables 2–11) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Limitation of the review . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
102 102 102 102 102 102 102 103 103 103 103 103 103 103 103 103 103 103 106 106
夽 AsianAOMS: Asian Association of Oral and Maxillofacial Surgeons; ASOMP: Asian Society of Oral and Maxillofacial Pathology; JSOP: Japanese Society of Oral Pathology; JSOMS: Japanese Society of Oral and Maxillofacial Surgeons; JSOM: Japanese Society of Oral Medicine; JAMI: Japanese Academy of Maxillofacial Implants. ∗ Corresponding author. Tel.: +91 4426801583; mobile: +91 9940482260. E-mail addresses: [email protected], [email protected] (J.S. Jesudasan). 2212-5558/$ – see front matter © 2013 Asian AOMS, ASOMP, JSOP, JSOMS, JSOM, and JAMI. Published by Elsevier Ltd. All rights reserved.夽 http://dx.doi.org/10.1016/j.ajoms.2013.05.014
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9.
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Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9.1. Implications for practice . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9.2. Implications for research . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1. Background Dry socket was first described as a complication of disintegration of the intra-alveolar blood clot, with an onset 2–4 days after extraction. According to Fazakerlev and Field [1], the alveolus empties, the osseous surroundings are denuded and covered by a yellow-grey necrotic tissue layer, and the surrounding mucosa usually becomes erythematous. It is clinically characterised by a putrid odour and intense pain that radiates to the ear and neck [2]. Pain is considered the most important symptom of dry socket. It can vary in frequency and intensity, and other symptoms, such as headache, insomnia, and dizziness, can be present. Calhoun [3] also reported trismus as a frequent symptom that develops 10–40 days after extraction, if the infection does not spread. Regional lymphadenopathy can be present on the affected side, and fever is infrequent. Dry socket is commonly observed in patients 40–45 years old [4,5]. Published data have reported an incidence of 1–4% after teeth extraction, with an incidence 10 times greater for lower teeth than for upper teeth [6] and reaching 45% for mandibular third molars [7,8]. Recently, investigators have suggested the following definition for dry socket: postoperative pain surrounding the alveolus that increases in severity for some period from 1 to 3 days after extraction, followed by partial or total clot loss in the interior of the alveolus, with or without halitosis [9,10]. Numerous methods and techniques are proposed throughout the existing literature to assist with prevention of alveolar osteitis (AO). Systemic antibiotics reported to be effective in the prevention of AO include penicillins, clindamycin, erythromycin, and metronidazole [11,12]. A great number of studies have been performed in order to test the effectiveness of topical medicaments in preventing AO. Several studies have reported that the pre- and perioperative use of 0.12% chlorhexidine [13–15] decreases the frequency of AO after mandibular third molar removal. Lagares et al. used chlorhexidine gel on the reduction of the incidence of impacted third molar post-extraction dry socket alveolitis [16]. Early literature reported that the topical use of para-hydroxybenzoic acid (PHBA) [17,18] an antifibrinolytic agent in extraction wounds, decreased the incidence of AO. Some authors have suggested copious intraoperative lavage to reduce the incidence of AO. Butler and Sweet [8,19] reported significant reduction in AO when 175 ml lavage was used as compared to 25 ml lavage. Bloomer et al. suggest that placement of medicated dry socket packing immediately after lower third molar extraction decreases the alveolar osteitis rate [20].
106 106 106 107
• Extractions should be performed with minimum amount of trauma and maximum amount of care. • Wherever possible preoperative oral hygiene measures to reduce plaque levels to a minimum should be instituted [23]. • Encourage the patient (again) to stop or limit smoking in the immediate postoperative period. • Advise patient to avoid vigorous mouth rinsing for the first 24 h post extraction and to use gentle toothbrushing in the immediate postoperative period. • For patients taking oral contraceptives extractions should ideally be performed during days 23 through 28 of the menstrual cycle [19]. • Comprehensive pre- and postoperative verbal instructions should be supplemented with written advice to ensure maximum compliance. 2.2. Pharmacological interventions • • • • • •
Antibacterial agents. Antiseptic agents and lavage. Antifibrinolytic agents. Steroid anti-inflammatory agents. Obtundent dressings. Clot support agents.
2.3. Based on the first dictum of medicine As stated by Hippocrates (421 BC): ‘At first do no harm’, it seems prudent to limit the pharmacological preventive interventions to measures which are supported by sufficient evidence to be effective, and equally, show a minimum of side effects. Some authors have promoted the use of eugenol containing dressing to prevent development of AO [20,24–27]. Despite many years of research, little progress has been made in addressing this commonly encountered and unpleasant postoperative condition in patients. Why it is important to do this review? Although a variety of treatment methods have been available for alveolar osteitis, there appears to be a paucity of large randomised studies comparing the treatments for alveolar osteitis. There is therefore little research which accurately compares the different interventions with each other and no systematic review has previously been done in this area.
3. Structured question 2. Summary of various treatment options A variety of treatment techniques have been described in the literature [17].
• Does eugenol have any effect in the management of alveolar osteitis (AO)? 3.1. Pico analysis
2.1. Non pharmacological methods [21] • Use of good quality current preoperative radiographs. • Careful planning of the surgery. • Use of good surgical principles [22].
• Population—patients with alveolar osteitis or at risk of developing AO. • Intervention—eugenol. • Control—various management options of AO.
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• Outcome—post operative pain, infection, wound healing, exposed bone, halitosis, unpleasant taste, redness around the socket and debris. 3.2. Types of outcome measures Primary outcome measure was Preoperative and Postoperative pain. Secondary outcomes included infection, wound healing, exposed bone, halitosis, unpleasant taste, redness around the socket and debris but these outcomes varied according to different studies. 4. Materials and methods 4.1. Sources used In July 2012 search for relevant trials in The Cochrane Library, MEDLINE and PUBMED(MESH) was done. Fig. 1. Search strategy: self-explanatory.
4.2. Search strategy Search strategy was developed in accordance with the guidelines outlined in the Cochrane handbook for systematic reviews. Search was done in Cochrane library (1995–July 2012), PUBMED (till 2012) and MEDLINE. The search was widened to include the internet and hand searched reference lists of identified articles. No language restrictions were imposed on the search. To maximise the identification of relevant articles we used the key phrase ‘alveolar osteitis’ and all the other possible related terms to alveolar osteitis and in second search the keywords ‘alveolar osteitis’ and all the other possible related terms to the management of management of alveolar osteitis were searched. All the search terms were included in the appendix given later. The flow chart that follows shows the search strategy of obtained four articles which met the inclusion criteria.
Table 1 Variables of interest. S. no.
Variables of interest
1 2 3
Pre and postoperative pain Other outcomes/method of evaluation Risk of bias
four randomised control trials that were included in this study as per inclusion criteria (Table 1). 5. Results Only four randomised control trials met the inclusion criteria of this review.
4.3. Inclusion criteria
5.1. General information of included studies (Tables 2–11)
Only randomised control trials that used eugenol in management of alveolar osteitis were included in the review. Both males and females and patients of all age who were affected by alveolar osteitis were considered in this study and only human studies of English language were included.
Graphs to show the comparison between eugenol and various other management modalities with regard to postoperative pain as given in the four studies (Figs. 2–5).
4.4. Exclusion criteria The following studies were excluded: • Case reports/case series/cohorts/clinical trials/animal studies, etc. • Studies not in English. • Studies not meeting the inclusion criteria. 4.5. Search flow chart Flow chart shows search strategy (Fig. 1). 4.6. Search results Review of titles and abstracts identified from the searches were done. If it was clear that the study did not refer to randomised control trial then it was excluded. If it was unclear then the full text was obtained and the list of excluded studies were mentioned and reason for exclusion were mentioned. An independent literature search carried out by two of the investigating author’s revealed only
6. Discussion This systematic review examines from 4 RCTs the effect of eugenol in the management of AO. In all of the selected trials a total of 86 patients out of 219 patients used eugenol in the management of AO. Eugenol was compared with other material like Salicept patch, saline irrigation and curettage, thermosetting gel, lasers, GECB and dextranomer granules. According to Kaya et al. [24]. The baseline clinical examinations revealed severe pain in all patients (n = 104; 100%). Other signs and symptoms included halitosis (n = 78, 75%), debris (n = 62, 60%), an empty socket (n = 60, 58%), redness around the socket (n = 50, 48.1%), exposed bone (n = 50, 48.1%), and an unpleasant taste in the mouth (n = 29, 28%). The differences in the changes in the clinical signs and symptoms between the control group and all three treatment groups were statistically significant (P = 0.05) on the third day after treatment. LLLT group showed better results than the other three groups. Alvogyl (eugenol) group was better than irrigation and curettage but no statistical difference was seen between it and the Salicept group. The decrease in pain was significantly greater for the LLLT group than for the alvogyl, Salicept, and control groups. According to Burgoyne et al. [25], the mean pretreatment pain score was 6.72 on a scale ranging from 1 to 10 for the eugenol
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Table 2 Characteristics of included study of Kaya et al. [24]. Methods
Single centre (Department of Oral and Maxillofacial Surgery, Atatürk University)
Participants Interventions
104 Patients with complaint of alveolar osteitis from January 2008 to July 2009 The patients were randomly assigned to 4 groups of 26 patients each Group 1 (control group; 15 women and 11 men), curettage and irrigation alone Group 2 (12 women and 14 men), curettage and irrigation followed by alvogyl applied directly to the socket Group 3 (15 women and 11 men), curettage and irrigation followed by Salicept applied directly to the socket Group 4 (11 women and 14 men), curettage and irrigation followed by LLLT irradiation (808 nm, 100-mW continuous mode gallium aluminium arsenide diode laser Relative decrease in signs and symptoms Preoperatively: Group 1: n = 4, Group 2: n = 4.23, Group 3: n = 4.62, and Group 4: n = 4.69 Postoperatively: Group 1: n = 1.62, Group 2: n = 0.62, Group 3: n = 0.36, and Group 4: n = 0.08 No statistical difference in the management of AO was seen between Groups 2 and 3. However, it was significantly better in Group 4 than the other three groups
Outcomes
Results
Table 3 Risk of bias (Kaya et al. [24]). Item
Author’s judgement
Description
Adequate sequence generation Allocation concealment Blinding all outcomes
Yes Unclear No
Incomplete outcome data addressed? All outcomes
No
Randomisation done Insufficient information to permit judgement Participants and clinicians were not blinded–intervention Administration vs. observation only. Not clear whether outcome assessors were blinded All the 104 patients were initially randomised. And the outcomes were measured. No patients were missing during the follow up
Table 4 Characteristics of included study of Burgoyne et al. [25]. Methods
Single centre (Department of Oral and Maxillofacial Surgery, School of Dentistry, Virginia Commonwealth University, Richmond, VA)
Participants Interventions
35 Patients with alveolar osteitis Group A: There were 5 males and 15 females (Control) Group B: There were 8 males and 7 females (treatment) Visual analogue scale for pain Preoperative mean value. Group A: 6.72 and Group B: 6.37 Postoperative mean value. Group A: 3.2 ± 0.62 and Group B: 4.83 ± 0.43 The efficacy of the two treatments was not significantly different
Outcomes
Results
Table 5 Risk of bias (Burgoyne et al. [25]). Item
Author’s judgement
Description
Adequate sequence generation Allocation concealment Blinding all outcomes
No Unclear No
Incomplete outcome data addressed? All outcomes
No
Not mentioned clearly Insufficient information to permit judgement Participants and clinicians were not. Not clear whether outcome assessors were blinded All the 35 patients were initially randomised. And the outcomes were measured. No patients were missing during the follow up
Table 6 Characteristics of included study of Haghighat et al. [27]. Methods
Single centre (Maxillofacial Surgery Department Of Isfahan University Of Medical Sciences)
Participants Interventions
30 Patients diagnosed with dry socket syndrome after impacted lower third molar extraction were selected Group 1: 15 patients (11 males and 4 females) undergone treatment with ZOE Group 2: 15 patients (7males and 8 females) were treated with pastille GECB Duration of pain after treatment. Group 1: Pain persisted for 45.53 ± 33.34 min. Group 2: 19.87 ± 21.80 min GECB showed more significant efficacy in reducing complications than ZOE
Outcomes Results Table 7 Risk of bias (Haghighat et al. [27]). Item
Author’s judgement
Description
Adequate sequence generation Allocation concealment Blinding all outcomes
No Unclear No
Incomplete outcome data addressed? All outcomes
No
Not mentioned clearly Insufficient information to permit judgement Participants and clinicians were not blinded. Not clear whether outcome assessors were blinded All the 30 patients were initially randomised. And the outcomes were measured. No patients were missing during the follow up
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Table 8 Characteristics of included study of Majati et al. [26]. Methods
Single centre (K.L.E.V.K. Institute of Dental Sciences, Belgaum, India)
Participants Interventions
A sample of 50 patients was studied Group A: Received zinc oxide eugenol dressing Group B: Received dextranomer dressing Control of pain and promotion of wound healing Group A: pain relief with statistically significant t value. 6.5248 Group B: pain relief with statistically significant t value. 4.8980 Statistically significant result was in favour of dextranomer dressing
Outcomes
Results
Table 9 Risk of bias (Majati et al. [26]). Item
Author’s judgement
Description
Adequate sequence generation Allocation concealment Blinding all outcomes
No Unclear No
Incomplete outcome data addressed? All outcomes
No
Not mentioned clearly Insufficient information to permit judgement Participants and clinicians were not. Not clear whether outcome assessors were blinded All the 50 patients were initially randomised. And the outcomes were measured. No patients were missing during the follow up
Fig. 4. Study 3. Haghighat et al. [27]. X axis, time in minutes taken to reduce pain and Y axis, different management modalities used by the author. GECB and eugenol.
Fig. 2. Study 1: Kaya et al. [24]. X axis, number of patients; Y axis, different management modalities used by the author; C&I, curettage and irrigation; eugenol, Alvogyl; Salicept, Salicept patch; and LLLT, low level laser treatment.
Fig. 5. Study 4: Majati et al. [26]. X axis, number of days taken for pain relief and Y axis, different management modalities used by the author. Dextranomer granules and ZOE. Table 10b Level of evidence according to the United Kingdom National Health Service. Fig. 3. Study 2: Burgoyne et al. [25]. X axis, pain score (VAS 1–10) and Y axis, different management modalities used by the author. Thermosetting gel and eugenol.
Table 10a Level of evidence according to the United States Department of Health and Human Services. S. no.
Author
Year
Design
Level of evidence
1 2 3 4
Kaya et al. [24] Burgoyne et al. [25] Haghighat et al. [27] Majati et al. [26]
2011 2010 2012 2010
RCT RCT RCT RCT
1 1 1 1
S. no.
Author
Year
Design
Level of evidence
1 2 3 4
Kaya et al. [24] Burgoyne et al. [25] Haghighat et al. [27] Majati et al. [26]
2011 2010 2012 2010
RCT RCT RCT RCT
Level A Level A Level A Level A
group and 6.37 for the prilocaine-lidocaine group with no statistical difference. In the immediate post-treatment period (0–15 min) the pain levels were significantly reduced in both groups. However, the thermosetting gel produced a significantly greater reduction in pain (mean, 3.23; SE, 0.62) than the eugenol (mean, 4.83; SE, 0.43). Over the next 48 h, the pain level was nominally less with the thermosetting gel, but this difference was not statistically significant.
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Table 11 Summation table for individual parameters of all four studies. Study 1: Kaya et al. [24]
Signs, symptoms Pre op pain Post op pain Unpleasant taste Halitosis Empty socket Exposed bone Redness Debris Healing
Study 2: Burgoyne et al. [25]
Study 3: Haghighat et al. [27]
Study 4: Majati et al. [26]
Eugenol
Curettage and irrigation
Salicept
LLLT
Eugenol
Thermosetting gel
Eugenol
GECB
Eugenol
4.3 26n 6n 0n 2n 2n 1n 1n 2n *
4 26n 23n 2n 3n 0n 1n 12n 2n *
4.62 26n 3n 0n 2n 1n 0n 0n 0n *
4.69 26n 1n 0n 0n 0n 0n 0n 1n *
* 6.72 VAS 4.83 VAS * * * * * * *
* 6.37 VAS 3.23 VAS * * * * * * *
* 8.33 VAS 45.53 min * * * * * * 45.53 min
* 8.27 VAS 19.87 min * * * * * * 9.87 min
* * 4.2 days * * * * * * 5.3 days
VAS, visual analogue scale (1–10); min, time in minutes; days, duration in days; n, number of patients; *, no data available relating to this.
According to them although the efficacy of the two treatments was not significantly different, the nominal superiority and ease of using the thermosetting gel warranted further investigation. Majati et al. [26] said that statistically significant results with respect to pain control and initial healing were obtained in favour of dextranomer dressing. They also said that mean period for complete pain relief was 4.2 days with zinc oxide eugenol dressing as against 2.8 days with dextranomer dressing and Mean period for initial healing was 5.3 days in zinc oxide dressing as against 3.5 days in dextranomer dressing. They said that this could be attributed to its absorbent action which removes local kinins, exudates, bacteria and toxins which are responsible for causing pain by irritating the free nerve endings. According to Haghighat et al. [27], pain persisted for 45.53 ± 33.34 min in patients treated with ZOE and 19.87 ± 21.80 min in those treated with GECB. They also said that patients in the ZOE group reported more painkiller intake within 20 days. They concluded that because of GECB pastille convenience and its one session use with less chair time, compared to ZOE, it can be an effective and reliable alternative for traditional ZOE method. 7. Summary Does eugenol have an effect in the management of alveolar osteitis? According to the review conducted with the four RCT’s there is no doubt that eugenol has an effect in the management of alveolar osteitis. According to Kaya et al. [24], Alvogyl (eugenol) group was better than irrigation and curettage but no difference was seen between it and the Salicept group. They concluded that in their study LLLT was the best option among the management options they compared for AO. Burgoyne et al. [25] said that the pain levels were significantly reduced in both groups that they compared (both the eugenol and the thermosetting gel groups). According to the study by Majati et al. [26] they said that significant results with respect to pain control and initial healing were obtained in favour of dextranomer dressing over eugenol but suggested further larger studies to obtain more conclusive results. Haghighat et al. [27] concluded that because of GECB pastille convenience and its one session use with less chair time, compared to ZOE, it can be an effective and reliable alternative for traditional ZOE method. In all the four trials a total of 219 patients out of which 86 patients were administered eugenol for the management of AO. Eugenol was found to be more effective than curettage and irrigation and equal to thermosetting gel and Salicept. Eugenol was
found to be less effective than low level laser, GECB and dextranomer granules. 8. Limitation of the review In spite of a large number of studies identified by this review, the quality of follow-up data and assessment variables for the effect of eugenol in the management of AO were limited. The majority of the studies do not provide a statistical analysis of the variables that were used. Furthermore, there is inconsistency in literature regarding a definitive management for AO. The few studies that compared eugenol with other modalities don’t provide the necessary data to draw stronger conclusions. Of the studies included in this review, complications were rarely addressed and therefore the lack of unmatched studies in this regard may lead to a bias. Furthermore the small sample of qualifying articles may mask the presence of significant results. The studies identified were generally small with an average of 30 cases per study. The numbers of cases eligible for analysis were further restricted by the way in which data had been published. We also acknowledge the potential presence of publication bias within this review. Owing to the small numbers of studies included, an assessment could not be performed in greater detail. No unpublished data was included. 9. Conclusion 9.1. Implications for practice Although good quality research exists on the efficacy of different treatment modalities of AO only four suitable Randomised control trial were obtained following a literature search by two different investigators regarding the effect of eugenol in the management of AO. All the studies showed post-operative decrease in pain and complications with the use of eugenol. Hence we conclude that eugenol is a viable and safe option for the management of alveolar osteitis but not necessarily the best option when compared to other options available. 9.2. Implications for research a) There is a great need for well-designed randomised studies to evaluate the use of eugenol in AO. b) Such studies should preferably address all the following outcomes: pre and postoperative pain, rate of infection, wound healing, bone exposure, halitosis and complications. c) Standardised outcome measures would make studies easier to compare.
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d) The statistical power of the study will need careful consideration and problems with accuracy of sufficient numbers of participants will need to be addressed. A multicentre approach may need to be adopted if accuracy rates are likely to be low.
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