Impact of administration timing of subanesthetic doses of esketamine on emergence agitation in patients undergoing nasal endoscopic surgery: a randomized controlled trial

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Introduction Emergence agitation (EA) is a common complication following general anesthesia, particularly after nasal endoscopic surgery with nasal packing. This study investigated whether the administration timing of subanesthetic esketamine influences its efficacy in preventing EA. Methods In this randomized, double-blind, placebo-controlled trial registered at the China Clinical Trial Registry (No. ChiCTR2500115004), 108 adult patients undergoing elective nasal endoscopic surgery were randomized (1:1:1) to receive intravenous normal saline (Group C), esketamine 0.25 mg.kg⁻ 1 during anesthesia induction (Group E1), or esketamine 0.25 mg.kg⁻ 1 20 min before surgical completion (Group E2). The primary outcome was the incidence of EA in the post-anesthesia care unit (PACU), defined as a Riker Sedation-Agitation Scale (SAS) score ≥ 5. Secondary outcomes included SAS scores, postoperative NRS pain scores, hemodynamics, and adverse events. Results Ninety-five patients completed the study (Group C: n = 32; Group E1: n = 32; Group E2: n = 31). Baseline characteristics were comparable across groups. The overall EA incidence differed significantly among groups (13/32 [40.6%] in C, 8/32 [25.0%] in E1, 3/31 [9.7%] in E2; P = 0.018). Group E2 had a significantly lower EA incidence (absolute risk reduction [ARR], 30.9%, [95% CI, 11.0%–50.9%]; number needed to treat [NNT], 3.2 [95% CI, 2.0–9.1]; P = 0.011) and lower SAS scores (adjusted P = 0.016) than Group C, whereas Group E1 showed no significant difference compared with Group C ( P = 0.287). Postoperative pain scores, rescue analgesia, extubation time, PACU stay, hemodynamic stability, and adverse event rates were comparable across all groups. Conclusions The preventive effect of subanesthetic esketamine on EA is timing-dependent. Administration 20 min before the end of surgery (0.25 mg.kg⁻ 1 IV) significantly reduces EA incidence in nasal endoscopic surgery patients. However, this single-center finding requires multicenter validation, and NRS scales remain limited in capturing packing-related suffocation discomfort. Clinical Trial Registration identifier ChiCTR2500115004.