Comparing benzodiazepine-ketamine and benzodiazepine-fentanyl sedation in phacoemulsification: A double-blind crossover non-inferiority clinical trial (BEKEF study)

Background: Topical anesthesia for cataract surgery often requires adjunctive sedation to manage intraoperative discomfort and improve patient cooperation. Ketamine and fentanyl, combined with benzodiazepines, are commonly used sedation regimens, but their comparative safety and efficacy in the cataract surgery context remain underexplored. This study aimed to evaluate whether ketamine combined with midazolam is non-inferior to fentanyl combined with midazolam for sedation during phacoemulsification, with a non-inferiority margin of 10%. Methods: This prospective, double-blind, crossover, non-inferiority trial randomized 75 patients to receive both sedation regimens for bilateral phacoemulsification. A 15-day washout period was implemented between surgeries. Adequate sedation was defined as a Ramsay Sedation Scale score of 2-3. The primary outcome was sedation adequacy, with secondary outcomes including patient and surgeon satisfaction, surgical metrics, and complications. Results: Of the 75 randomized patients, 65 (130 eyes) completed the study. Adequate sedation was achieved in 86.2% of cases with ketamine and 89.2% with fentanyl, with a within-participant difference of 3.1% (95% CI:-2.3%-5.3%), confirming non-inferiority. Patient satisfaction scores were similarly high between regimens (ketamine: 4.87 f 0.36; fentanyl: 4.91 f 0.28; P = 0.45). Complications were infrequent, with two cases of nausea and two of bradycardia in the fentanyl group and one case of nausea and two of hypertension in the ketamine group. Conclusions: Ketamine combined with midazolam is a safe and effective alternative to fentanyl-based sedation for cataract surgery, providing comparable sedation quality and satisfaction. These findings support ketamine's use in cataract surgery.