Preoperative Oral Esketamine for Perioperative Comfort in Children Undergoing Adenotonsillectomy: A Randomized, Double‐Blind, Dose‐Finding Study

BACKGROUND: Pediatric adenotonsillectomy often causes preoperative anxiety, venous cannulation pain, and emergence agitation. Esketamine has multimodal properties, but the optimal oral dose for children is unknown. This study evaluated oral esketamine at 1, 2, and 3 mg/kg for perioperative comfort. METHODS: In this randomized double-blind trial, 99 children (ASA I-II, 1-6 years) received oral 10% glucose (control, n = 26) or esketamine 1 mg/kg (EK1, n = 26), 2 mg/kg (EK2, n = 23), or 3 mg/kg (EK3, n = 24) 30 min before anesthesia. PRIMARY OUTCOMES: Ramsay Sedation Scale (RSS) and FLACC pain score at venous cannulation, and PAED score at 15 min after extubation. SECONDARY OUTCOMES: remifentanil use, postoperative FLACC (2-48 h), sleep quality, and adverse events. RESULTS: All esketamine doses improved sedation and analgesia at cannulation (overall p < 0.001), with largest effect at 3 mg/kg. Median RSS (IQR): control 1.00 (1.00-2.00); EK1 2.00 (1.75-3.00, p = 0.028); EK2 2.00 (1.00-3.00, p = 0.049); EK3 3.00 (2.00-3.37, p < 0.001). FLACC scores: control 6.00 (3.00-7.00); EK1 2.50 (1.00-4.00, p = 0.016); EK2 2.00 (0.00-4.00, p = 0.001); EK3 0.00 (0.00-1.75, p < 0.001). PAED score at 15 min was lower in EK2 than control (5.00 [2.00-10.00] vs. 10.00 [6.00-12.00], p = 0.048). Remifentanil consumption was reduced in EK3 (120.00 [80.00-159.50] vs. 240.00 [160.00-315.00] μg, p = 0.001). Postoperative pain at 2-6 h was lower in EK2 and EK3 (p < 0.05), persisting to 48 h in EK3 (p < 0.05). Sleep quality improved in EK3 at 24 h (p = 0.023) and 48 h (p = 0.032). Adverse events did not differ significantly. CONCLUSIONS: Preoperative oral esketamine (1-3 mg/kg) enhances perioperative comfort in children undergoing adenotonsillectomy. The 2 mg/kg dose offers the best balance of efficacy and safety, while 3 mg/kg provides superior analgesia and opioid sparing.