Effects of chlorhexidine gluconate combined with benzydamine hydrochloride or flurbiprofen on pain, edema, and trismus following surgical extraction of impacted mandibular third molars

The aim of this study was to compare two chlorhexidine-containing topical formulations—KLOROBEN ® (chlorhexidine gluconate + benzydamine hydrochloride) and KLORHEX PLUS ® (chlorhexidine gluconate + flurbiprofen)—following the surgical extraction of bilateral mesioangular impacted mandibular third molars, with respect to postoperative pain, swelling, and trismus. A total of 40 volunteer patients (20 males and 20 females; age range: 18–50 years) with bilateral mesioangular impacted mandibular third molars were enrolled in this randomized, triple-blinded, split-mouth clinical trial. In each patient, one impacted third molar was surgically extracted and a randomly assigned topical agent was applied to the surgical site. After a four-week healing interval, the contralateral tooth was extracted and the alternate topical agent was administered following the same protocol. The primary outcome was maximum interincisal distance on postoperative day 7. Secondary outcomes included postoperative pain (VAS), facial edema, and analgesic consumption. Clinical assessments of trismus and facial edema were performed on postoperative days 2 and 7, while pain and analgesic consumption were recorded at predefined intervals during the 7-day follow-up. Pain was evaluated using the Visual Analog Scale (VAS), trismus was assessed by measuring maximum interincisal distance, and swelling was determined using standardized facial measurements (tragus-pogonion, tragus-labial commissure, mandibular angle-lateral canthus). No statistically significant differences were observed between the two topical agents regarding postoperative pain levels, facial swelling, or analgesic consumption at any evaluated time point ( p > 0.05). However, a statistically significant difference was observed between the groups in maximum mouth opening on postoperative day 7, with higher values in the chlorhexidine–flurbiprofen group (40.33 ± 6.46 mm) compared to the chlorhexidine–benzydamine group (38.90 ± 6.84 mm) ( p < 0.05). Both chlorhexidine gluconate–benzydamine and chlorhexidine gluconate–flurbiprofen formulations demonstrated comparable outcomes with respect to postoperative pain, facial swelling, and analgesic consumption following surgical removal of impacted mandibular third molars. A statistically significant difference in maximum interincisal distance was observed on postoperative day 7 in favor of the chlorhexidine–flurbiprofen group; however, the clinical relevance of this finding should be interpreted with caution. These findings represent a direct comparison between the two chlorhexidine-containing formulations and do not establish additional benefit over chlorhexidine alone or superiority to standard postoperative care. ClinicalTrials.gov NCT07416136, registered in February 2026. Retrospectively registered.