EFFICIENCY OF TOPICAL OZONE GEL AS AN ADJUNCT TO ANTIBIOTICS AND ANALGESICS ON SEQUELAE AFTER EXTRACTION OF IMPACTED MANDIBULAR THIRD MOLAR

Introduction: Extraction of the impacted mandibular third molar is a common procedure in dentistry. Many complications may arise after this operation, the most common being pain, trismus, and swelling. Systemic medications have been used in an attempt to manage these problems, but because of their side effects, the need for non-medication treatment arises to treat these complications without side effects, such as cryotherapy, ice packs, low-level laser therapy, and ozone. Ozone is one of the most effective antimicrobials used in the dentistry field, and it also has a positive effect on soft tissue healing, activates cellular metabolism, and can react with blood components; for these reasons ozone is used to manage trismus, swelling, and pain after removal of the mandibular third molar. Aim: The purpose of the study was to assess the effects of topical ozone gel on complications from the extraction of the impacted mandibular third molar. Materials and Methods: Thirty patients were enrolled in the current study and were randomly divided into two equal groups. Preoperatively clinical examination included measurement of facial swelling measurements and maximum mouth opening. The position and configuration of the impacted lower third molar, the surrounding bone, the mandibular canal, and the neighboring tooth were all assessed using a panoramic X-ray. On days 2 and 7, after surgery, the facial swelling dimensions and maximum mouth opening were again assessed. Statistics were used to analyze results. Results: Findings indicate statistical significance for pain, but not for swelling or mouth opening. Conclusions: After lower third molar surgery, topical ozone gel helps reduce postoperative pain.


INTRODUCTION
One of the most frequent operations in the field of oral and maxillofacial surgery is third molar surgery.However, this intervention warrants precise planning and surgical experience.Complications with surgical operations in general are always possible.
Between 2.6 percent and 30.9 percent of third molar extraction, procedures result in complications.The range of possible issues ranges from moderate, normal postoperative pain and swelling to irreversible nerve damage, mandibular fractures, and life-threatening infections. 1,2e most prevalent third molar surgery complications are limited mouth opening, pain, and edema.Pain reaches maximum intensity between three to five hours after local anesthesia has worn off, continues for two to three days, and gradually reduces until the 7 th day. 3 Swelling reaches peak intensity in 12-48 h, resolving between the 5 th and 7 th day. 4 Trismus subsides when pain and edema decrease. 5They are regarded as the result of tissue damage or infection-related inflammation.Systemic medications such as antibiotics, glucocorticoids, and analgesics, have been used in attempts to manage these problems and achieve satisfactory postoperative recovery. 2,6e use of surgical closure procedures with or without the incorporation of drains, cold packs, platelet-rich plasma, platelet-rich fibrin, herbals, and cryotherapy have been recommended as nonpharmacological adjunctive therapies, 7-12 but due to their limited effectiveness and accompanying side effects, they have not been widely adopted.
Ozone therapy and low-level laser therapy (LLLT) have been introduced as these alternatives over the past 20 years.The stratosphere of the Earth contains Ozone (O 3 ) in its gaseous state, with a molecular weight of 48 grams/mol.As a result of changes in temperature and pressure, it is an unstable gas that is regularly converted into oxygen (O 2 ). 13,14Research on this subject supports the use of ozone in the fields of medicine and dentistry.This recommendation is given due to its special effects on the human body, such as its effective antimicrobial action (fungicidal, bactericidal, and virucidal).[17][18] Ozone can be applied topically or parenterally 19 and is available as a gas, gel, or liquid. 20Ozone therapy's therapeutic success may partly be attributed to the regulated oxidative stress brought on by the reactions of ozone with various biological elements.Ozone can interact with blood components in the right amounts to positively impact oxygen metabolism and cell energy while also triggering antioxidant defense mechanisms. 21Ozone therapy has been utilized in dentistry to treat temporomandibular joint dysfunction, 25,26 endodontic, 23 and periodontal diseases, 24 as well as caries. 22ditionally, this treatment has been appli- In this study, the impact of intra-oral topical ozone therapy was assessed on the postoperative parameters of pain, trismus, and edema as well as patient ozone tolerance.However, the gel form was selected for our study because of advantages, 29 such as ease of application, the existence of a higher concentration of ozone molecules, and the compound's stability for a longer time.Ozone gel may be produced and stored without the use of a complicated arsenal, unlike ozone gas.Additionally, it has been demonstrated that aqueous ozone preserves cell biology more effectively than gaseous ozone. 30Ozone is present in the gel in the form of ozonides, which release active ozone over an extended time when in contact with a wound surface at the temperature of body.

Study population
This study was conducted at the Oral Surgery

Study design
This blind placebo-controlled randomized prospective clinical study involved 30 patients, 12 male and 18 female, aged between 18 and 36 years, with lower im-pacted third molars in similar positions (Class II-III and B position, according to Pell and Gregory's classification).They were randomly assigned to the study and control groups using the coin toss method, divided in two equal groups, with fifteen patients in each.Group (1) (study group): injection of ozone gel (0.5cc) after removal of impacted mandibular third molar.Group (2) (control placebo group): removal of the impacted mandibular third molar followed by 0.5cc of normal saline was injected into the socket as shown in the flow chart (Figure 4).

At baseline
1. Radiographic and clinical examination.

Measurements of mouth openings were
assessed by measuring the maximum distance between the cutting edges of the maxillary and mandibular central incisors.
The mouth opening was measured three times using a digital Vernier.3. Facial measurement, the distances between the lateral corner of the eye and the mandibular angle (line A), the tragus and the outer corner of the mouth (line B), and the tragus and soft tissue pogonion (line C) were measured using a measuring tape and recorded in centimeters, 32 (Figure 5).
The average of the three different values of line A, line B, and line C was calculated and reflected the swelling for that day. 33,34he difference between measurements taken before surgery and each postoperative measurement done on the 2 nd and 7 th days was recorded.

At first recall
On the 2 nd day, the same measurement at baseline was repeated in addition to the measurement of pain using a numeric rating scale (NRS), the intensity of the pain was estimated.Whose ratings range from zero (absence of pain) to ten (the most severe pain conceivable).

On the second recall
On the 7 th day, the same measurement on the first recall.Third-molar extractions were performed using local anesthesia, which was obtained by inferior alveolar, lingual, and long buccal nerve block injection using the (lidocaine hydrochloride 2% local anes-thetic cartridge 1.8ml with adrenaline 1:80,000 (Septodent®, France).
A three-sided mucoperiosteal flap was then made, and bone was removed using a round bur in a surgical straight handpiece (Castellini®, Germany) with copious saline irrigation to expose the tooth, Following the extraction of the tooth, the surgical site was adequately irrigated using a normal saline solution (0.9%) then the flap was repositioned, and the wound was stitched.From the incision to the final suturing, the time required for the tooth along the different observation periods for all groups.

RESULTS
Thirty patients with asymptomatic lower impacted third teeth participated in the trial.These had a mean age of 23.4±4.8 years (range, 18-36 years), (Table 1).Thirty tooth extractions were carried out without complications.The average procedure time was 35.92±7.1 min for the control group and 35.6±4.8 min for the ozone group (p>0.05),measuring the duration between the initial surgical incision and the final closure using sutures, (Table 2).
Eleven impacted teeth were classified as cl II and 19 impacted teeth as cl III by Pell and Gregory (p>0.05).Sixteen mesioangulation, eight vertical, three horizontal, and three distoangulation of impacted teeth (p>0.05),(Table 3).
All patients experienced primary healing and no abnormal bleeding throughout the procedures.There was no ecchymosis or hematoma-related alteration in skin color.
None of the patients had any negative reactions to the medication or ozone therapy.
Recalled patients had their pain, edema, and trismus assessed.In all assessments (Table 4), the NRS ratings for the ozone group were substantially lesser than those for the control (placebo) group (p-values of 0.039 and 0.016 for the second and seventh postoperative days, respectively). 2 patients in the ozone group did not require analgesics.
Both groups experienced trismus and postoperative edema.There was no noticeable difference between the study group and the control group in terms of trismus (Table 5) and edema (Table 6) on the second and seventh days (p>0.05).

DISCUSSION
One of the most effective antimicrobials utilized in the dentistry field is ozone, which is bactericidal, veridical, and fungicidal. 35e cell membrane is damaged and disrupted, and the intracellular components are broken down and oxidized, all of which have bactericidal effects.In just a few 10-20 seconds, it eradicates 99% of microflora.Reverse transcriptase inhibits the synthesis of proteins of viral in viruses, and it affects cell development negatively in fungi at selective stages. 36,37a 3500 times more quickly and effectively than chlorine, ozone may kill and eliminate bacteria. 38It has rheological characteristics, 39 activates cellular metabolism, 30 and stimulates the expression of cytokines as well as increases intracellular ATP (adenosine triphosphate) concentration. 40 particular, the transforming growth factor-B1 (TGF-B1) has a positive impact on the healing of soft tissue injuries. 41In addition to improving oral soft tissue repair, these growth Additionally, the initial postoperative phase protective layer of ozone gel above the area of surgery may prevent wound contamination and also covers the exposed nerve ends, greatly lowering pain.
The current study's findings revealed that all groups experienced the most pain during the first two days following surgery.There was a significant difference between the days in each group after that, with the pain score tending to diminish over time until the seventh day.
When comparing to the control (placebo) group, the study group's pain scores decreased (p-0.05) on the second and seventh days.
The results of this study are in agreement with those of Kazancioglu et al., 16 Sivalingam et al., 20 Silva et al., 45 and Bahl et al., 53 who showed that ozone can lessen postoperative pain following surgical removal of the mandibular third molar.However, ozone had no beneficial effect on pain, per the findings of research carried out by Gloria et al. 46 The results of the current study indicated that ozone had no statistically significant impact on trismus.The difference among the groups was, however, statistically not significant (p>0.05).On the 7 th postoperative day, patients in the ozone group had nearly reached their preoperative mouth opening value, even though the difference among the groups was statistically insignificant.Within the control group, this was not the case.
Ozone's analgesic and biosynthetic qualities aid in better wound healing, which is why the ozone group returned to healthy mouth opening more quickly than other groups.

HypothesisH0:
The ozone gel is not-significantly effective in reducing swelling, pain, and trismus following extraction of the mandibular impacted third molar.H1: The ozone gel is significantly effective in the reduction of swelling, trismus, and pain following extraction of the lower impacted third molar.Aim: This clinical trial aims to evaluate ozone gel on pain, trismus, and swelling after removal of impacted mandibular third molar.
Department at the College of Dentistry/ University of Babil and the Oral Surgery Clinic at the specialized center in Babil government between March and August of 2022.Participants were registered volunteers for the study after signing the informed consent sheet to participate in the research study and submitted to a questionnaire comprising their name, age, gender, medical history, and dental history followed by a complete clinical and radiographic examination.Inclusion criteria Patients with impacted mandibular third molars (Class II-III and position B, according to Pell and Gregory's classification) who required surgical extraction, should have good oral hygiene, be free of any acute illnesses, and be between the ages of 18 and 40.They should also be willing to comply with the study and be available for follow-up.Exclusion criteria Ozone therapy contraindications, systemic illness, local infection, tobacco use, and pregnancy were among the exclusion criteria.All patients signed a written informed consent after being given information re-garding the study's purpose, the specifics of the surgical procedures, any expected complications, and potential adverse effects of the medications being used.Following surgery, the patients were given Augmentin® 625 mg (amoxicillin 500mg and 170 Alhelu OA, Mahdi ZF & Saadi Abdulhameed B. Efficiency of topical ozone gel as an adjunct to antibiotics and analgesics on sequelae af ter extraction of impacted mandibular third molar.J Oral Res.2023; 12(1): 168-181.https://doi.org/10.17126/joralres.2023.015clavulanate 125mg) and Panadol® 500 mg (acetaminophen) as needed.

Figure 1 :
Figure 1: Pell and Gregory classification of the third molar.

Table 2 .
Descriptive and statistical test of surgical duration among groups.

Table 3 .
Demographic data among groups.
a: Fisher´s exact test.b: chi square

Table 5 .
p-values and mean values ±SD of mouth opening (measured in millimeters)

Table 6 .
p-values and mean values ±SD of facial swelling dimensions (in millimeters) along the different observation periods for all groups.

20, 47
50cording to Schultze-Mosgau et al.,50facial edema was measured in the current study, and no appreciable difference was seen between 177 Alhelu OA,

Mahdi ZF & Saadi Abdulhameed B. Efficiency of topical ozone gel as an adjunct to antibiotics and analgesics on sequelae af ter extraction of impacted mandibular third molar. J Oral Res. 2023; 12(1): 168-181. https://doi.org/10.17126/joralres.2023.015 the
16ntrol and study groups.While Alkholy et al.,51reported no statisti-cally significant difference in trismus between the study and control groups, Yousef et al.,52and Sivalingam et al.,20found that there is a beneficial effect of ozone on swelling, in disagreement with the result of this study, which is in agreement with the results reported by Kazancioglu et al.,16who found there is no beneficial effect of ozone on swelling.Ozone as a supportive therapy may be use-ful in lowering pain, but it was ineffective in the reduction of trismus and swelling, according to the findings of the current study.It is impossible to provide a practical suggestion for employing ozone as a supportive therapy to reduce trismus, pain, and swelling in lower third molar extractions due to the limits of this research and the extremely low certainty of the studies' findings.To increase the certainty of the evidence, more standardized protocols must be established for this therapy.Future research should therefore be done to clarify the effect of ozone therapy in the practice of oral surgery. 178CONCLUSION