BackgroundKetamine gargle is considered a highly effective measure for preventing postoperative sore throat (POST). This randomized controlled study aimed to explore the efficacy, safety, and optimal dosage of esketamine gargle for preventing POST following laryngeal mask airway insertion.MethodsA total of 150 patients were randomly assigned to receive normal saline (NS), 25 mg, or 50 mg of esketamine gargle at a 1:1:1 ratio for 30 s prior to general anesthesia. The primary outcomes were the incidence of POST at 2, 6, and 24 h postoperatively. The secondary outcomes included the severity of POST at 2, 6, and 24 h postoperatively, along with the incidence and severity of dysphagia and hoarseness. Other outcomes included the incidence of the first intubation attempt, repositioning during surgery, convert to tracheal intubation, SpO2 < 90%, blood stain on the laryngeal mask airway, tachycardia and hypertension following gargling, intraoperative peak airway pressure, and end - tidal carbon dioxide partial pressure (PetCO2).ResultsThe incidence of POST at 2, 6, and 24 h postoperatively was 32%, 10%, and 12%; 22%, 8%, and 8%; and 12%, 6%, and 4%, respectively, with a statistically significant difference among groups at 2 h postoperatively (P = 0.007). In comparison with the NS group, the incidence of POST at 2 h postopertively in the 25 mg group was significantly lower (32% vs. 10%, P = 0.013). No statistically significant differences were observed in the remaining outcomes.ConclusionEsketamine gargle is effective and safe for preventing POST following laryngeal mask airway insertion, and a dose of 25 mg is recommended.Clinical Trial RegistrationChiCTR2500099787.