Efficacy of hyaluronic acid spray on swelling, pain, and trismus after surgical extraction of impacted mandibular third molars


The aim of this study was compare the efficacies of two oral sprays in reducing swelling, pain, and trismus after the extraction of impacted mandibular third molars. This prospective double-blind, randomized, crossover clinical trial included 34 patients with bilateral symmetrically impacted mandibular third molars of similar surgical difficulty. Hyaluronic acid or benzydamine hydrochloride spray was applied (two pumps) to the extraction area, three times daily for 7 days. Swelling was evaluated using a tape measure method, pain with a visual analogue scale (VAS), and trismus by measuring the maximum inter-incisal opening. Assessments were made on the day of surgery and on days 2 and 7 after surgery. Statistically significant differences were detected for the swelling and trismus values between the two treatment groups on the second postoperative day ( P = 0.002 and P = 0.03, respectively). However, there was no statistically significant difference in VAS scores between the two groups. The administration of hyaluronic acid spray was more effective than benzydamine hydrochloride spray in reducing swelling and trismus. Although no evidence of a reduction in pain levels was detected, hyaluronic acid appears to offer a beneficial effect in the management of swelling and trismus during the immediate postoperative period following impacted third molar surgery.

The surgical extraction of impacted third molars is one of the most common procedures in oral and maxillofacial surgery. Patients refer to the postoperative swelling, pain, and trismus associated with the inflammatory response to surgical trauma as the main factors affecting their daily life. There are several other complications associated with the extraction of impacted third molars, the most common being alveolar osteitis and postoperative infection, which can be a burden for both the patient and the surgeon.

To prevent or reduce postoperative inflammation and associated symptoms, adequate anti-inflammatory therapy is needed. Corticosteroids and anti-inflammatory drugs are the options most often used to ameliorate these postoperative symptoms. Corticosteroids are used widely to decrease the oedema and trismus related to third molar surgery. The potential side-effects of perioperative corticosteroid use are adrenal suppression, delayed wound healing, and increased susceptibility to infection.

Hyaluronan or hyaluronic acid (HA) is a biomaterial that has been introduced as an alternative approach to enhance wound healing. HA is a major carbohydrate component of the extracellular matrix and can be found in many tissues. It has multifaceted roles in biology, utilizing both its physicochemical and biological properties, and also has many properties that make it a potentially ideal molecule for assisting wound healing: inducing beneficial early granulation tissue formation, inhibiting destructive inflammation during the healing phase, and promoting re-epithelialization and also angiogenesis. By virtue of its non-immunogenicity and non-toxicity, its use has been established in many medical disciplines, such as ophthalmology, dermatology, and rheumatology. The synthetic form of HA for topical oral use is available in a gel or liquid preparation.

Benzydamine hydrochloride (BnzHCl) is a non-steroidal drug with analgesic, anti-inflammatory, and antimicrobial properties. Its mechanism of action is not entirely known, but the drug may affect the formation of thromboxanes and alter the rate of prostaglandin production, thereby inhibiting platelet aggregation and stabilizing cell membranes. It is often recommended for the relief of inflammatory conditions of the oral cavity and is commonly used as a mouth rinse or mouth spray at a concentration of 0.15%.

The aim of this study was to compare the efficacies of HA and BnzHCl sprays in reducing swelling, pain, and trismus after the surgical extraction of impacted mandibular third molars.

Materials and methods

Patient selection

This study was a prospective double-blind, randomized, crossover clinical trial. The study received approval from the institutional ethics committee. Forty patients were enrolled in the study and provided a signed statement of informed consent. All patients had bilateral symmetrically impacted mandibular third molars. Thirty-four patients (15 male, 19 female; mean age 23.35 ± 3.89 years) completed the study.

Patients with no systemic disease, history of allergy, or bleeding problems, those who co-operated with the study and with postoperative follow-up, and those who had bilateral symmetrically impacted mandibular third molars with total or partial bone cover and of comparable surgical difficulty were included in the study.

The following patients were excluded from the study: those with signs of pericoronitis and/or pain before surgery, those who were pregnant or nursing a baby, those in whom the extraction of the retained third molar lasted for more than 30 min or the operation time differed by more than 5 min between the two sides, those who had undergone antibiotic or other medication therapies during the preceding 2 weeks, those who had active carious lesions and/or periodontal diseases, and those who had contraindications to the drugs or anaesthetics used in the surgical protocol.

Study design

All of the patients were operated on by the same experienced oral and maxillofacial surgeon and assistant in order to minimize differences due to operator variability. Each patient underwent two surgical operations, separated by 4 weeks. In the first operation, the right third molar was extracted. The patients were divided randomly into two groups: after the operation the patient was given either BnzHCl spray (Tanflex oral spray, 30 ml, 0.15% BnzHCl; Abdi Ibrahim Pharmaceutical Company, Istanbul, Turkey) or HA spray (Gengigel spray 50 ml, 0.2% HA; Farmalink Saglik Urunleri San. ve Tic. Ltd. Sti., Istanbul, Turkey) and instructed to apply the spray, two pumps to the extraction area three times a day, for 7 days. In the second operation, the left third molar was extracted and the other spray was given to the patient. Both the surgeon and the patient were blinded to the spray given. The patients were instructed not to eat or drink for 1 h after the use of both sprays.

Surgical protocol

All patients underwent the procedure under inferior alveolar and buccal nerve blocks using articaine with 1:200,000 epinephrine. A three-cornered flap was raised to gain access to the third molar, and buccal osteotomy and sectioning were carried out when necessary. Once the tooth had been extracted, the alveolus was irrigated with sterile saline solution at room temperature to eliminate debris and the bone edges were smoothed; the flap was then repositioned and the closure was performed with 3–0 silk. All patients received prophylactic antimicrobial and non-steroidal anti-inflammatory/analgesic drugs, and written postoperative instructions. The postoperative medication for both groups was 1 g amoxicillin two times a day and 550 mg naproxen sodium every 8 h for 4 days.

The degree of surgical difficulty was rated before the extractions by a single investigator, who performed the preoperative patient selection. The Pederson scale was used for this purpose ; the extractions were classified as easy, moderate, or difficult ( Table 1 ).

Table 1
Criteria and scores of the Pederson scale.
Criteria Score
1. Spatial relationship
Mesioangular 1
Horizontal/transverse 2
Vertical 3
Distoangular 4
2. Ramus relationship
Class 1: sufficient space 1
Class 2: reduced space 2
Class 3: no space 3
3. Depth
Level A: high occlusal level 1
Level B: medium occlusal level 2
Level C: low occlusal level 3
Difficulty score
Difficult 7–10
Moderate 5–6
Easy 3–4

The degree of facial swelling was determined by a modification of the tape measure method described by Gabka and Matsumara. Three measurements were made between five reference points: the distance between the lateral corner of the eye and angle of the mandible, the distance between the tragus and soft tissue pogonion, and the distance between the tragus and outer corner of the mouth. The mean of these three measurements was calculated. Measurements were taken preoperatively and on postoperative days 2 and 7.

Pain intensity was assessed using a 10-point visual analogue scale (VAS), with the patient placing a mark on the scale to indicate an intensity range from no pain ‘0’ to severe/unbearable pain ‘10’. The severity of the pain was evaluated on the operation day and on postoperative days 2 and 7.

Trismus was evaluated by measuring the distance between the edges of the upper and lower right central incisors at maximum opening of the jaws preoperatively and on days 2 and 7 after surgery.

All of the data obtained were evaluated using SPSS 15.0 package program (SPSS Inc., Chicago, IL, USA). Data were analyzed as the frequency and percentage rate, and as the mean and standard deviation. The Student t -test and repeated measures tests were performed for parametric continuous data. A significance level of P < 0.05 for the 95% confidence interval was chosen to define statistical significance.


Thirty-four patients (15 male, 19 female; mean age 23.35 ± 3.89 years) completed the present study. Six of the initially enrolled 40 patients were excluded from the study: two did not return for the second surgery, one did not complete the questionnaire, and for three patients, the difference between the operation times of the two sides was more than 5 min.

The impacted mandibular third molars on the left and right sides of the patients were comparable with respect to the degree of surgical difficulty. There was no significant difference in the difficulty score for mandibular third molar impaction between the sides (mean difficulty score for the right side 6.44 ± 0.92 and for the left side 6.50 ± 0.99; t = −0.25; P = 0.80).

On the second postoperative day, facial swelling was significantly increased in both groups when compared to preoperative measurements; however, the facial swelling in the HA group was lower than that in the BnzHCl group and the difference between the two groups was statistically significant ( P 0.002). By the seventh postoperative day, facial swelling in both groups was minimal and there was no statistically significant difference between the two groups ( Table 2 ).

Table 2
Measurement of swelling (mean ± SD in mm; n = 34).
Groups Preoperative Second day Seventh day Repeated measures
HA 11.25 ± 0.51 12.81 ± 0.83 11.54 ± 0.65 F = 65.45
P = 0.000
BnzHCl 11.44 ± 0.65 13.36 ± 0.56 11.70 ± 0.74 F = 45.84
P = 0.000
t and P values t = −1.31
P = 0.20
t = −3.18
P = 0.002
t = −0.98
P = 0.33
SD, standard deviation; HA, hyaluronic acid; BnzHCl, benzydamine hydrochloride.

With regard to the mean VAS scores, pain was highest on the operation day and decreased gradually in both groups on postoperative days 2 and 7. There were no statistically significant differences in VAS scores between the two groups on the day of the operation or on postoperative days 2 and 7 ( Table 3 ).

Table 3
Comparison of VAS scores (mean ± SD; n = 34).
Groups Operation day Second day Seventh day Repeated measures
HA 7.08 ± 1.46 3.52 ± 1.54 1.32 ± 0.68 F = 988.30
P = 0.000
BnzHCl 7.14 ± 1.23 3.64 ± 1.04 1.47 ± 0.61 F = 1613.25
P = 0.000
t and P values t = 0.18
P = 0.86
t = −0.37
P = 0.71
t = −0.93
P = 0.36
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Jan 19, 2018 | Posted by in Oral and Maxillofacial Surgery | Comments Off on Efficacy of hyaluronic acid spray on swelling, pain, and trismus after surgical extraction of impacted mandibular third molars
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