Abstract
Objective:
The objective of this study was to assess the efficacy of ozone gas (O3) on the reduction of dry socket (DS) occurrence following surgical extraction of lower jaw third molars, influence of the indication for the extraction, and the difficulty of extraction on the incidence of DS.
Materials and Methods:
This study included thirty patients with bilaterally impacted third molars of mandible requiring surgical procedure for extraction. Following extraction, in the control group, saline solution was used for irrigation of extraction sockets and in the experimental group, intra-alveolar O3 was applied for 12 s (Prozone, W and H, UK, Ltd.). The surgeries were performed by the same oral surgeon. The follow-up visits were performed at 48 h and on day seven, postsurgery where the symptoms of DS were evaluated and intensity of pain has been recorded using visual analog scale 0–100.
Results:
In this pilot study, DS was present in 16.67% and 3.33% of cases in the control and experimental groups, respectively (P = 0.20).
Conclusion:
The application of O3 may reduce the incidence of DS and accelerates the recovery period after the surgery. Prophylactic use of O3 may be suggested in all patients, especially in the patients at a risk of development of DS.
Keywords: Dry socket, ozone gas, third molar
INTRODUCTION
Dry socket (DS) is one of the most common complications following third molar surgery. Its exact etiology and pathogenesis, despite various approaches to this pathology, are still not known. DS was originally described as a consequence of disintegration of blood clot during days 2–4 after the tooth extraction. Its appearance has been described based on the clinical symptoms, such as a dry alveola covered with a layer of necrotic, yellow-gray tissue, halitosis, and high intensity of pain that radiates to the neck and ear.[1,2] Although rare, other symptoms are lymphadenitis, headache, insomnia, and trismus, as described in the literature.[3,4]
Ozone gas (O3) is an agent with powerful antimicrobial action.[5,6] It has helpful use as a disinfectant in the field of medicine and dentistry and has been used widely in all fields of dentistry. Atabas D found that treatment with ozone combined with re-mineralizing solution or either alone is very effective to the initial fissural caries lesions.[7] In clinical terms, O3 can be applied in three basic forms such as gaseous, water, and oil for treating various pathologies. Prozone (W and H, UK, Ltd.,) is a new technology that produces ozone in a gaseous state for use in various dental applications. It generates O3 and regulates its flow of concentrations, so they do not exceed the permitted therapeutic values. O3 has several actions in the human body as an antibacterial, anti-inflammatory, and immunostimulatory agents by utilizing the body's oxygen metabolism and also stimulates the antioxidant humoral system of human organisms.[8] Its antibacterial effect is based on its ability to form oxidizing free radicals and destruction of microorganisms.[8] It promotes its antioxidant potential in the destruction of cytoplasmic membranes and cell walls of bacteria, blocking the system enzyme of the cell. This action results in increased permeability of the cell membrane, causing immediate termination of all of its functions and death of microorganisms. This action is selective in microorganisms’ cells, but not in human cells because of the human body's greater antioxidant capacity of cells and inhibition, which is vital to stave off the uncontrolled activity of free radicals.[9,10]
The objectives of our study were as follows:
To determine the effect of gaseous O3 in reducing the presence of DS following bilateral surgical lower jaw third molar extraction compared to the control group
Influence of the indication for the extraction on the incidence of DS by groups
Influence of the difficulty of extraction on the incidence of DS by groups.
MATERIALS AND METHODS
This pilot study was performed in the Department of Oral Surgery in the University Dental Clinical Centre of Kosovo (UDCCK) which included thirty patients addressed in our clinic for surgical extraction in the period of January 2014–June 2014. The Ethics Committee of UDCCK approved the research protocol. Before the surgery, all patients signed an informed consent for participation in the study.
Inclusion criteria were the following: Age 18–30 years; bilateral impacted lower third molars in similar position verified by orthopantomography; and an indication for surgical extraction (pericoronitis, caries, pulpitis, or orthodontic indication). Exclusion criteria included the following: Any systemic disease; smokers; immunocompromised patients; pregnant women; and those who were taking contraceptives.
Surgical procedure
Randomization was used to determine which side would comprise the control group (Gr1) and which would comprise the experimental (O3) group (Gr2). The patients were not aware of these designations. All the surgeries were performed by the same oral surgeon. Local analgesia was achieved using 4 ml of 2% lidocaine with 1:80,000 adrenalines (Alkaloid, Skopje, Macedonia). A triangular, full-thickness buccal flap was elevated for bone exposure. Bone osteotomy was performed for the section of the tooth if required. Afterward, 5 ml of 0.9% saline solution (Gr1) or O3 gas (Gr2) was used to irrigate the socket. We used Prozone equipment to supply the O3 gas, which enabled us to introduce the gas into the socket using plastic attachments for 12 s calibrating the therapeutic dose. This procedure was performed using a surgical suction unit to avoid respiratory aspiration and related complication. Suturing was performed with 3/0 absorbable suture (Ethicon, Somerville, NJ, USA).
The patients were then given postoperative instructions and prescribed ibuprofen 400 mg as an analgesic/anti-inflammatory drug. Postoperative visits were scheduled for 48 h after the surgery and on postoperative day 7. Additional appointments were made as needed. Clinical examination was performed to find evidence of one or more of the following main objective signs of a DS: Absence of a blood clot, bone exposure, or necrotic blood clot. We also recorded the number of analgesic tablets ingested.
Subjective clinical findings included patient data of persistent postoperative pain after the surgery. The degree of pain was recorded on a visual analog scale.
Statistical analysis
Data analysis was performed using Pearson's χ2 test, Fisher's exact test (P), and McNemar's test. P < 0.05 was considered to indicate statistical significance.
RESULTS
The mean age of the patients was 21.87 ± 4.11 years (95% confidence interval [CI]: 20.33–23.40) [Table 1].
Table 1.
Age of all participants in the study Group 1/Group 2

The incidence of DS in Gr1 (n = 5; 16.67%) was higher than that in Gr2 (n = 1; 3.33%), but with no significant difference (P = 0.20) [Table 2].
Table 2.
Incidence of dry socket in the Group 1/Group 2

In the Gr1, the incidence of DS was higher in those who underwent very difficult surgery and in those requiring osteotomy with resection during the tooth extraction compared with those without tooth or root resection. The only case of DS in the Gr2 was recorded in a patient whose tooth extraction was very difficult (osteotomy, root, and tooth resection required) [Table 3].
Table 3.
Influence of the difficulty of extraction on the incidence of dry socket Group 1/Group 2 Difficulty of extraction DS, n (%) T

No adverse reactions were recorded during the study implementation.
According to indications for removing the tooth, the frequency of DS was higher in cases of orthodontic versus pericoronitis indications [Table 4].
Table 4.
Influence of the indication for extraction on the incidence of dry socket Group 1/Group 2

The number of consumed analgesics within 48 h after surgery was 3.07 ± 1.96 tablets (95% CI: 2.33–3.80) in Gr1 and 1.20 ± 1.16 tablets (95% CI: 0.77–1.63) in Gr2. The minimum number of consumed analgesics was 0 and the maximum number was 6 in Gr1 and 0 and 4, respectively, in Gr2 [Table 5].
Table 5.
Number of tablets consumed within 48 h after surgical extraction Group 1/Group 2

DISCUSSION
Overall complication following third molar surgery rates of about 10%[11] including pain, secondary infection of the head and neck region, dislocation of third molars, excessive bleeding, temporary or permanent damage to the cranial nerves, and mandibular fracture was reported by Yadav et al.[12] DS is one of the most challenging complications after surgical extraction of lower third molars. The role of bacteria in the development of DS has been discussed in many clinical and scientific studies. This concept is based on research results that confirmed the increased DS frequency in patients with pericoronitis, poor oral hygiene, and periodontal disease.[13] Potential interference of Actinomyces viscosus and Streptococcus mutans in DS has been studied by Rozanis et al. and it is demonstrated in experimental models of delayed socket recovery after inoculation of these microorganisms.[14] Increasing the number of pyrogenic bacteria as activators of indirect fibrinolysis creates ideal conditions for blood clot disintegration and DS development. Interference of bacteria in the development of DS by introducing preventive antibiotics explains the reduced incidence in many clinical research studies.[15,16,17,18] Akota et al. demonstrated a significant reduction in the incidence of DS after the application of chlortetracycline-impregnated gauze compared with a control group.[19] Nitzan et al. observed increased fibrinolytic activity by Treponema pallidum which is present in periodontal disease,[20] explaining why children, who are not colonized by this bacterium, do not develop DS.
The results of our research showed the efficacy of gaseous O3 in reducing the incidence of DS after surgical extraction of lower third molars compared with the saline solution. Our results also showed that the control patients consumed a large number of analgesic tablets 48 h after tooth extraction compared with the patients who were given O3, with the difference reaching statistical significance (P < 0.01).
Based on our results, intensity of pain following third molar surgical extraction in cases where gaseous O3 was applied was significantly less than in cases where only saline solution was used for irrigation. This can be explained by the fact that O3 helps in the synthesis of biologically active substances as leukotrienes, interleukins, and prostaglandins, which are beneficial in reducing inflammation and pain.[21,22] O3 activates angiogenesis in inflamed tissue[23,24] by reacting with blood elements (erythrocytes, leukocytes, platelets, and vascular system). It also has a positive impact on oxygen metabolism, cellular energy, and the antioxidant defense system in the blood microcirculation, thereby improving oxygen delivery to hypoxic tissues by stimulating its metabolism. In addition, it has been found that ozone could accelerate wound healing and bone reparative processes.[25]
Applying O3 to the socket following tooth extraction promotes faster healing of the wound without complications.[26] O3 also reduce the period of recovery by forming a pseudomembrane in the socket that protected it from mechanical and physical insults.[27] It has also been proved to be useful in the treatment of refractory osteomyelitis as a complementary therapy to antibiotics and oxygen hyperbaric application[8,28,29] and promoting the bone healing.[30]
CONCLUSION
According to our findings, O3 gas has a positive effect on reducing the development of DS and pain following third molar surgery. The microbiological and metabolic capabilities of O3 for promoting hemostasis, increasing the supply of oxygen, and inhibiting bacterial proliferation increase the opportunities for its use in all fields of surgery. Further clinical trials are needed with larger samples to support our conclusion.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
REFERENCES
- 1.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. doi: 10.1016/s0278-2391(89)80110-7. [DOI] [PubMed] [Google Scholar]
- 2.Fazakerley M, Field EA. Dry socket: A painful post-extraction complication (a review) Dent Update. 1991;18:31–4. [PubMed] [Google Scholar]
- 3.Sasaki T, Okamoto T. Topical treatment of infections of alveolar socket infections following dental extraction. Rev Bras Odontol. 1968;25:82–92. [PubMed] [Google Scholar]
- 4.Calhoun NR. Dry socket and other postoperative complications. Dent Clin North Am. 1971;15:337–48. [PubMed] [Google Scholar]
- 5.Tuncay Ö, Dinçer AN, Kustarci A, Er Ö, Dinç G, Demirbuga S. Effects of ozone and photo-activated disinfection against Enterococcus faecalis biofilms in vitro . Niger J Clin Pract. 2015;18:814–8. doi: 10.4103/1119-3077.163289. [DOI] [PubMed] [Google Scholar]
- 6.Boch T, Tennert C, Vach K, Al Ahmad A, Hellwig E, Polydorou O. Effect of gaseous ozone on Enterococcus faecalis biofilm an in vitro study. Clin Oral Investig. 2015 Dec 4; doi: 10.1007/s00784-015-1667-1. Epub ahead of print. [DOI] [PubMed] [Google Scholar]
- 7.Atabek D, Oztas N. Effectiveness of ozone with or without the additional use of remineralizing solution on non-cavitated fissure carious lesions in permanent molars. Eur J Dent. 2011;5:393–9. [PMC free article] [PubMed] [Google Scholar]
- 8.Loncar B, Mravak Stipetic M, Matosevic D, Tarle Z. Ozone application in dentistry. Arch Med Res. 2009;40:136–7. doi: 10.1016/j.arcmed.2008.11.002. [DOI] [PubMed] [Google Scholar]
- 9.Ozone Therapy in Dentistry. [Last accessed on 2016 Jun 06];J Nat Sci Biol Med. 2011 2:151–3. doi: 10.4103/0976-9668.92318. Available from: http://www.absoluteozone.com/ozone-therapy-in-dentistry.html . [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Makkar S, Makkar M. Ozone treating dental infections. Indian J Stomatol. 2011;2:256–9. [Google Scholar]
- 11.Valmaseda-Castellón E, Berini-Aytés L, Gay-Escoda C. Inferior alveolar nerve damage after lower third molar surgical extraction: A prospective study of 1117 surgical extractions. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2001;92:377–83. doi: 10.1067/moe.2001.118284. [DOI] [PubMed] [Google Scholar]
- 12.Yadav S, Tyagi S, Puri N, Kumar P, Kumar P. Qualitative and quantitative assessment of relationship between mandibular third molar and angle fracture on North Indian population: A clinico-radiographic study. Eur J Dent. 2013;7:212–7. doi: 10.4103/1305-7456.110188. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Rud J. Removal of impacted lower third molars with acute pericoronitis and necrotising gingivitis. Br J Oral Surg. 1970;7:153–60. doi: 10.1016/s0007-117x(69)80015-6. [DOI] [PubMed] [Google Scholar]
- 14.Rozanis J, Schofield ID, Warren BA. Is dry socket preventable? Dent J. 1977;43:233–6. [PubMed] [Google Scholar]
- 15.Contar CM, Oliveira P, Kanegusuku K, Silva BR, Azevedo Alanis LR, Machado MA. Complications in third molar removal: A retrospective study of 588 patients. Med Oral Patol Oral Cir Buccal. 2010;15:74–8. doi: 10.4317/medoral.15.e74. [DOI] [PubMed] [Google Scholar]
- 16.Curran JB, Kennett S, Young AR. An assessment of the use of prophylactic antibiotics in third molar surgery. Int J Oral Surg. 1974;3:1–6. doi: 10.1016/s0300-9785(74)80030-x. [DOI] [PubMed] [Google Scholar]
- 17.Halpern LR, Dodson TB. Does prophylactic administration of systemic antibiotics prevent postoperative inflammatory complications after third molar surgery? J Oral Maxillofac Surg. 2007;65:177–85. doi: 10.1016/j.joms.2006.10.016. [DOI] [PubMed] [Google Scholar]
- 18.Ritzau M, Hillerup S, Branebjerg PE, Ersbøl BK. Does metronidazole prevent alveolitis sicca dolorosa. A double-blind, placebo-controlled clinical study? Int J Oral Maxillofac Surg. 1992;21:299–302. doi: 10.1016/s0901-5027(05)80743-x. [DOI] [PubMed] [Google Scholar]
- 19.Akota I, Alvsaker B, Bjørnland T. The effect of locally applied gauze drain impregnated with chlortetracycline ointment in mandibular third-molar surgery. Acta Odontol Scand. 1998;56:25–9. doi: 10.1080/000163598423027. [DOI] [PubMed] [Google Scholar]
- 20.Nitzan D, Sperry JF, Wilkins TD. Fibrinolytic activity of oral anaerobic bacteria. Arch Oral Biol. 1978;23:465–70. doi: 10.1016/0003-9969(78)90078-x. [DOI] [PubMed] [Google Scholar]
- 21.Moezizaden M. Future of dentistry, nanodentistry, ozone therapy and tissue engineering. J Dev Bio Tissue Eng. 2013;5:1–6. [Google Scholar]
- 22.Sujatha B, Manoj Kumar MG, Pratap Gowd MJ, Vardhan R. Ozone therapy – A paradigm shift in dentistry. Health Sci. 2013;2:3. [Google Scholar]
- 23.Seidler V, Linetskiy I, Hubálková H, Stanková H, Smucler R, Mazánek J. Ozone and its usage in general medicine and dentistry. A review article. Prague Med Rep. 2008;109:5–13. [PubMed] [Google Scholar]
- 24.Gupta G, Mansi B. Ozone therapy in periodontics. J Med Life. 2012;5:59–67. [PMC free article] [PubMed] [Google Scholar]
- 25.Adeyemo WL, Ogunlewe MO, Ladeinde AL, Abib GT, Gbotolorun OM, Olojede OC, et al. Prevalence and surgical morbidity of impacted mandibular third molar removal in the aging population: A retrospective study at the Lagos University Teaching Hospital. Afr J Med Med Sci. 2006;35:479–83. [PubMed] [Google Scholar]
- 26.Arita M, Nagayoshi M, Fukuizumi T, Okinaga T, Masumi S, Morikawa M, et al. Microbicidal efficacy of ozonated water against Candida albicans adhering to acrylic denture plates. Oral Microbiol Immunol. 2005;20:206–10. doi: 10.1111/j.1399-302X.2005.00213.x. [DOI] [PubMed] [Google Scholar]
- 27.Haensler RV. 4th Edition. Heidelberg: Karl F. Haug Publishers; 2002. The Use of Ozone in Medicine. [Google Scholar]
- 28.Agapov VS, Shulakov VV, Fomchenkov NA. Ozone therapy of chronic mandibular osteomyelitis. Stomatologiia (Mosk) 2001;80:14–7. [PubMed] [Google Scholar]
- 29.Steinhart H, Schulz S, Mutters R. Evaluation of ozonated oxygen in an experimental animal model of osteomyelitis as a further treatment option for skull-base osteomyelitis. Eur Arch Otorhinolaryngol. 1999;256:153–7. doi: 10.1007/s004050050130. [DOI] [PubMed] [Google Scholar]
- 30.Alan H, Vardi N, Özgür C, Acar AH, Yolcu Ü, Dogan DO. Comparison of the effects of low-level laser therapy and ozone therapy on bone healing. J Craniofac Surg. 2015;26:e396–400. doi: 10.1097/SCS.0000000000001871. [DOI] [PubMed] [Google Scholar]