Preventive Effect of Preoperative Intranasal Dexmedetomidine for Postoperative Delirium in Elderly Patients with Sleep Disorders Undergoing Major Noncardiac Surgery: A Randomized, Triple-Blind, Placebo-Controlled Trial

Purpose: Postoperative delirium (POD) is frequent and consequential in older adults, especially those with preexisting sleep disorders. While perioperative intravenous dexmedetomidine may lower POD risk, the benefit of preoperative intranasal administration is unknown. This study aimed to determine whether preoperative intranasal dexmedetomidine reduces POD in elderly patients with sleep disorders undergoing major noncardiac surgery. Patients and Methods: In this randomized, triple-blind, placebo-controlled trial, 348 elderly patients (≥ 60 years) with a Pittsburgh Sleep Quality Index > 7 undergoing major noncardiac surgery were enrolled between November 2023 and August 2024. Participants received either intranasal dexmedetomidine (n=174) or placebo (n=174) the night before surgery (20:30– 00:00). Dexmedetomidine was administered using a weight-based regimen (≤ 45 kg: 45 μg; 45– 75 kg: 60 μg; ≥ 75 kg: 75 μg), with a rescue dose of 30 μg allowed if sleep onset did not occur within 30 minutes. The primary outcome was the incidence of POD within 5 days postoperatively. Secondary outcomes included preoperative sleep quality, delayed neurocognitive recovery (dNCR) at 7 and 30 days postoperatively, and adverse events on the night before surgery. Results: The incidence of POD was significantly lower in the dexmedetomidine group than in the placebo group (18.4% vs 32.8%, RR:0.56, 95% CI:0.38– 0.82, P =0.002). Preoperative dexmedetomidine also improved sleep quality on the night before surgery, including total sleep time (6.2± 1.5 hours vs 5.3± 1.7 hours, mean difference:0.89, 95% CI:0.56– 1.23, P < 0.001), sleep efficiency (77.3%± 16.0% vs 66.3%± 19.1%, mean difference:11.01%, 95% CI:7.3%-14.7%, P < 0.001), and subjective sleep quality as assessed by the Richards-Campbell Sleep Questionnaire (68 ± 13 vs 59 ± 15, mean difference:9.31, 95% CI:6.35– 12.27, P < 0.001). There was no between-group difference in dNCR at day 7 or day 30 (both P > 0.05). Dexmedetomidine was associated with a higher incidence of bradycardia during the preoperative night (37.9% vs 16.7%; RR:2.28, 95% CI:1.55– 3.34, P < 0.001), while the incidence of other adverse events was similar between groups (all P > 0.05). Conclusion: Preoperative intranasal dexmedetomidine reduced the incidence of POD and enhanced preoperative sleep quality in elderly patients with sleep disorders undergoing major noncardiac surgery. Given the increased risk of bradycardia, these benefits should be weighed against the need for perioperative monitoring. Keywords: geriatric anesthesia, sleep quality, neurocognitive disorders, delirium prevention, alpha-2 adrenergic agonists