U ORALNOJ HIRURGIJI ANALYSIS OF EFFICACY OF ADDING DEXAMETHASONE TO ROPIVACAINE IN ORAL SURGERY

Uvod: Duža postoperativna anestezija postiže se upotrebom lokalnih anestetika dugog dejstva,kao što su ropivakain i bupivakain. U različitim hirurškim granama, duži bezbolni postoperativni period postiže se kombinacijom ropivakaina sa deksametazonom. Cilj rada bio je utvrditi kakav efekat na dužinu trajanja lokalne anestezije ima kombinacija 0,75% ropivakaina sa dodatkom deksametazona u toku i posle oralnohirurških operacija. Materijal i metode: Na Odeljenju oralne hirurgije Klinike za stomatologiju u Nišu, u toku 2017. godine, ispitivanjem je obuhvaćeno 12 pacijenata koji su podeljeni u 2 grupe: studijsku grupu od 6 pacijenata , koji su prilikom anestezije dobili 4 ml 0,75% rastvora ropivakaina i 1 ml deksazona od 4mg i kontrolnu grupu od 6 pacijenata koji su primili 4 ml 0, 75% rastvora ropivakaina. Statistička obrada podataka rađena je u programu SPSS 15.0. Rezultati:Vreme pojave prvih znakova anestezije, utvrđenih testom senzitivne osetljivosti mekih tkiva (usne i gingive) u studijskoj grupi bilo je 1,5 min, a u kontrolnoj 2,66 min. Vreme nastupanja potpune anestezije tj. potpune neosetljivosti mekih tkiva u studijskoj grupi bilo je 3,5 min, a u kontrolnoj 4,66 min. Vreme za koje su pacijenti još uvek osećali dejstvo anestezije u studijskoj grupi iznosilo je 625, 5 min što ima i statističku značajnost (p < 0.01), dok je u kontrolnoj grupi taj period bio oko 290 min. Zaključak: Male doze deksametazona dodatih lokalnom anestetiku mogu smanjiti potrebu za dodatnom anestezijom i analgetskom terapijom u prvia 24 sata posle teških oralno hirurških operacija.


Introduction
Pain is "an unpleasant sensory or emotional experience that results from actual or potential tissue damage" 1 and represents a subjective feeling that occurs in certain parts of the brain as a response to tissue damage or functional changes in the brain itself 2 .The nature and severity of pain are the consequences of sensory events that occur after damage to tissues and affective-cognitive mechanisms.
Local anesthetics are substances that temporarily block impulse conduction by nerve fibers and cause reversible anesthesia of the tissues that these fibers innervate, leading to the blockage of sodium channels and stabilization of the cell membrane of the nerve fibers 3 .
Ekenstam synthesized mepivacaine in 1957, as well as bupivacaine that later became the most used long-acting local anaesthetics 4 .Ropivacaine was synthesized the same year but had not been introduced into clinical practice before the early '90s 5 .
Since the first reports on the use of bupivacaine in oral surgery were published, this anesthetic was primarily used in surgery to ensure prolonged postoperative anesthesia.However, studies show that adrenaline added to bupivacaine increases its cardiotoxicity 6 .Intervascular or interosseous administration of bupivacaine may lead to acute cardiac arrest and patient death 7,8 .After adverse effects of bupivacaine had been reported (cardiovascular collapse, death following accidental intravenous administration), ropivacaine was introduced into clinical use in gynecology, orthopedics, urology, neurosurgery and other surgical branches for achieving regional anesthesia 9 .It was used for an oral surgery intervention at our clinic for the first time in 2003 10 .Ropivacaine is a long-acting local anesthetic of the amide group, chemically very similar to bupivacaine and mepivacaine.The efficacy of local anesthesia depends on the concentration of ropivacaine applied: 0.25%, 0.5% or 0.75%.The average duration of local anesthesia after the application of ropivacaine is between 4-5 hours [11][12][13][14] .Prolonged action of local anesthetics is particularly required after major oral surgeries as a way of reducing the use of analgesics in the postoperative period.Smatra se da je uvođenje glukokortikoida u terapiju jedno od deset najznačajnijih otkrića u modernoj medicini 15 .Dexametazon se koristi prvenstveno zbog imunosupresivnog, antiinflamatornog i antialergijskog dejstva.Antiinflamatorni efekat je posledica dejstva na različite ćelije koje su uključene u inflamatorni proces, jer glukokortikoidi dovode do smanjenja broja T limfocita, smanjenja fagocitne aktivnosti makrofaga i oslobađanja medijatora inflamacije iz makrofaga i T-limfocita 16 .
Svi pacijenti su bili obavešteni o sastavu lokalnog anestetika koji će primiti i oni su dali pisanu saglasnost za učešće u istraživanju.Pacijenti su posle operacije poneli sa sobom pisani upitnik u koji su unosili podatke o dužini dejstva anestezije u The introduction of glucocorticoids as a treatment is widely considered to be one of the ten most significant discoveries in modern medicine 15 .Dexamethasone is used primarily due to its immunosuppressive, anti-inflammatory and anti-allergic effects.The anti-inflammatory effect comes from its action on various cells involved in the inflammatory process which decreases the number of T lymphocytes, as well as the phagocytic activity of macrophages, and reduces the release of the inflammatory mediators from macrophages and Tlymphocytes 16 .
Numerous studies from different surgical branches show longer absence of pain after surgical intervention when ropivacaine is used with dexamethasone than when it is used alone [17][18][19][20] .To the best of our knowledge, there is no available data about using ropivacaine with dexamethasone in oral surgery.
The aim of this study was to determine the effect of adding dexamethasone to 0.75% ropivacaine on the duration of local anesthesia.

Materials and methods
Clinical examination of the duration of the local anesthetic -4ml of 0.75% ropivacaine solution (Ropivacaine Cabi, Phressenius, Greece) or 0.75% ropivacaine solution with the addition of 1 ml / 4 mg dexamethasone (Dexason, Galenika, Serbia) -was done in accordance with The Ethical Principles of The Helsinki Declaration on Patient Safety in Anesthesia 2010 21 .A total of 12 patients participated in the study which was conducted at the Department of Oral Surgery, Clinic of Dentistry Niš, in 2017.The patients belonged to ASA I 22 (healthy patients) and ASA II 22 group (patients with minor systemic changes, children, very old and obese patients, and patients with chronic bronchitis).Surgical interventions were performed on both the upper and lower jaw.The diagnosis and indication for oral surgery interventions was based on a clinical examination and a radiographic image (orthopantomogram).All patients were healthy, without any familiar history of chronic or acute illnesses and allergies to local anesthetics.All patients were informed about the components of the local anesthetic they were going to receive and they signed a written consent for participating in our research.Having undergone surgery, the patients were prva 24 sata po operaciji kao i o količini unetih analgetika.
given a written questionnaire about the duration of anesthesia in the first 24 hours, as well as the amount of analgesics they used in that period.
Patients were divided into two groups: the study group of 6 patients who received 4 ml of 0.75% ropivacaine solution with addition of 1 ml/4mg dexamethasone and the control group of 6 patients who received 4 ml of 0, 75% solution of ropivacaine without the addition of dexamethasone.Statistical data were processed by the SPSS 15.0 software.Continuous parameters were evaluated by a Student's ttest for Independent Samples.

Results
Out of 12 patients in total that were included in this study, 5(41.6%)patients were male and 7(58.45%) were female.The average age of patients was 27.8 years.Most of the oral surgery interventions performed were surgical removals of impacted wisdom tooth in the lower jaw -7(58,3%) out of 12 oral surgery interventions in total.
The onset time of the first signs of anesthesia, confirmed by testing sensibility of soft tissues (lip and gingiva), was 1.5 min in the study group and 2.66 in the control group.The time necessary for the full effect of anesthesia to set in, i.e. total insensitivity of soft tissues, was 3.5 min in the study group and 4.66 min in the control group.
The duration of local anesthesia, as measured by patients and described by numbness, partial or total insensitivity of lip, tongue or gingiva, was 625.5 min in the study group and 290 min in the control group (Table 2).The duration of anesthesia in the group that received a combination of 4 ml 0.75% ropivacaine and dexamethasone, 4mg/1ml (p < 0.01), was more than twice as long as that in the group that received only ropivacaine, which is considered statistically significant.Except for one patient who took a tablet of ibuprofen right after the intervention preventively, no other patients took analgesics in the first 24 hours postoperatively.

Discussion
A combination of 4ml 0.75% ropivacaine with 4mg/1ml dexamethasone resulted in successful perioperative and postoperative anesthesia of soft and bone tissues after major oral surgery interventions.In the study group, which received 4ml ropivacaine 0.75% with 4mg/1ml dexamethasone -administered in a single syringe, perioperative anesthesia lasted 625. 5 min, i.e 10.4 hours, while in the control group, which only received ropivacaine 0.75% it lasted 290 min, or 4.8 hours.
Dexamethasone is on the World Health Organization List of the Essential and Most Efficient Medicines in the Basic Health Care System 23 .It has an effect on the prolonged nerve block because it prevents the nociceptive transmission of the pulse along the myelinized C fiber 24,25 and acts locally on the nerve fiber, when applied perineurally 26 .Very often, a combination of different dosage of ropivacaine and dexamethasone (10 , 18, 25 ml ropivacaine and 4, 8 10 mg dexamethasone) is used to block the brachial plexus in shoulder surgery [27][28][29] , knee joint surgery 30 , hysterectomy 31 and for epidural anaesthesia 32 .The concentration used in this study, 4ml ropivacaine at a concentration of 0.75% and 1ml / 4mg of dexamethasone, which is considerably smaller than the dosage used by other authors, resulted in twice as long period of anesthesia.
Bupivacaine has also been combined with dexamethasone in some studies with the postoperative pain-free period lasting up to three times as long as without dexamethasone 33 .
Certain authors state that the duration of postoperative analgesia is dose dependent on the concentration of dexamethasone 35 , while others report contrasting results 36 .Some data suggest that combining glucocorticoids in the same syringe can lead to crystallization of liquids and potential organ embolism, while perineural administration can have a neurotoxic effect 37 .
In this study, dexamethasone and ropivacaine, administered in the same syringe, did not lead to the crystallization of the solution, or visible fluid clouding.The postoperative period with the combination used went without any symptoms of the neurotoxic effect or any negative systemic effects in all cases.
Considering the fact that there is no available information in the literature about perineural application (n.alveolaris inferior and rr.alveolares superiors posteriores) of ropivacaine in combination with dexamethasone in oral surgery, and that the combination dosage used in the study (4ml 0.75 % anesthesia and 1ml / 4mg Dexamethasone) was lower than the combination listed in the existing literature, our results show that this combination is equally successful in achieving perioperative and postoperative anesthesia in oral surgery as in other surgical branches [38][39] .

Conclusion
In oral surgery interventions where pain is expected after the intervention, a combination of 4 ml of ropivacaine 0.75% and 1 ml of dexamethasone 4 mg / ml, results in twice as long postoperative anesthesia (625.5 min) compared to ropivacaine only (290 min).It was noted that small doses of dexamethasone added to local anesthetics may reduce the need for additional anesthesia and analgesic therapy within the first 24 hours after major oral surgery interventions.

Table 1 .
Sex and the average age of patients

Table 2 .
Monitored parameters of anesthesia