Intranasal Dexmedetomidine-esketamine Combination and Postoperative Cognitive Recovery in Older Patients
Impact of Intranasal Dexmedetomidine-esketamine Combination on Neurocognitive Recovery in Older Patients After Noncardiac Surgery: a Randomized, Double-blind, and Placebo-controlled Trial
Postoperative neurocognitive disorders, including postoperative delirium (POD) and delayed neurocognitive recovery (dNCR), are common in older patients undergoing surgery and are associated with worse outcomes. Intranasal dexmedetomidine, esketamine, and their combination have been used in clinical practice to improve sleep quality and analgesia. A preliminary study suggested lower rates of emergence delirium and POD/dNCR in older patients receiving perioperative intranasal dexmedetomidine-esketamine. This randomized controlled trial is designed to test the hypothesis that perioperative administration of an intranasal dexmedetomidine-esketamine combination improves neurocognitive recovery in older patients undergoing noncardiac surgery.
研究概览
地位
详细说明
Postoperative neurocognitive disorders, including postoperative delirium (POD) and delayed neurocognitive recovery (dNCR), are common in older patients undergoing surgery and are associated with prolonged hospitalization, worse functional recovery, and increased mortality. Disturbed sleep is a modifiable contributor: perioperative sleep disruption may amplify neuroinflammation, pain, and opioid requirements, creating a feed-forward loop that promotes neurocognitive complications.
Dexmedetomidine, a highly selective α2-adrenergic agonist, mimics aspects of physiological non-rapid eye movement (NREM) sleep. Intranasal dexmedetomidine has been used to improve perioperative sleep in older patients. Esketamine, the S-enantiomer of ketamine, provides analgesia and has rapid antidepressant effects. Intranasal esketamine is approved for treatment-resistant depression. Combined use of subanesthetic doses of esketamine and dexmedetomidine shows synergy in analgesia and anxiolysis, with fewer neuropsychiatric adverse effects.
Combining low doses of both agents for intranasal administration therefore targets several mechanisms implicated in POD and dNCR simultaneously (sleep restoration, analgesia, anxiolysis, and potentially reduced opioid consumption) via a noninvasive route feasible on surgical wards. A preliminary study suggested lower rates of emergence delirium and POD/dNCR in older patients receiving perioperative intranasal dexmedetomidine-esketamine.
This randomized controlled trial is designed to test the hypothesis that perioperative administration of an intranasal dexmedetomidine-esketamine combination improves neurocognitive recovery in older patients undergoing noncardiac surgery.
研究类型
注册 (估计的)
阶段
- 第四阶段
联系人和位置
学习联系方式
- 姓名：Dong-Xin Wang, MD, PhD
- 电话号码：86 10 83572784
- 邮箱：wangdongxin@hotmail.com
研究联系人备份
- 姓名：Huai-Jin Li, MD
- 电话号码：86 10 83572460
- 邮箱：sophie.lee.coffee@gmail.com
学习地点
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Beijing Municipality
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Beijing、Beijing Municipality、中国、100034
- Peking University First Hospital
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接触：
- Huai-Jin Li, MD
- 电话号码：+8613488659162
- 邮箱：sophie.lee.coffee@gmail.com
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Inclusion Criteria:
- Age ≥65 years.
- Scheduled to undergo noncardiac surgery under general anesthesia with an expected operative duration >1 hour.
- Planned hospital stay of at least 1 day.
Exclusion Criteria:
- Nasal disease precluding intranasal administration (e.g., rhinitis, nasal polyps, or nasal congestion of any cause).
- Pre-existing schizophrenia, epilepsy, Parkinson's disease, or myasthenia gravis.
- Inability to communicate preoperatively due to coma, severe dementia, or language disorder.
- History of craniocerebral injury or neurosurgery.
- Pre-existing sleep-disordered breathing (diagnosed sleep apnea or high risk of moderate-to-severe sleep apnea on the STOP-Bang questionnaire).
- History of hyperthyroidism or pheochromocytoma.
- Preoperative LVEF <30%, sick sinus syndrome, severe sinus bradycardia (heart rate <50 beats/min), or second-degree or higher atrioventricular block without a pacemaker.
- Severe hepatic dysfunction (Child-Pugh class C), severe renal impairment requiring preoperative dialysis, or ASA physical status ≥IV.
- Planned postoperative ICU admission.
- Known allergy or hypersensitivity to dexmedetomidine and/or esketamine.
- Any other condition that, in the judgment of the investigator, makes the patient unsuitable for enrollment.
学习计划
研究是如何设计的？
设计细节
- 主要用途：预防
- 分配：随机化
- 介入模型：并行分配
- 屏蔽：四人间
武器和干预
参与者组/臂 |
干预/治疗 |
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实验性的：DEX-ESK group
Participants in this group will receive intranasal administration of a dexmedetomidine-esketamine combination at bedtime (8-9 pm) three times: the night before surgery, the night of surgery, and the first postoperative night. |
Participants in this group will receive intranasal administration of a dexmedetomidine-esketamine combination at bedtime (8-9 pm) three times: the night before surgery, the night of surgery, and the first postoperative night.
其他名称：
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安慰剂比较：Placebo group
Participants in this group will receive intranasal administration of placebo (0.9% saline) at bedtime (8-9 pm) three times: the night before surgery, the night of surgery, and the first postoperative night. |
Participants in this group will receive intranasal administration of placebo (0.9% saline) at bedtime (8-9 pm) three times: the night before surgery, the night of surgery, and the first postoperative night.
其他名称：
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研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
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Incidence of delayed neurocognitive recovery (dNCR) on postoperative day 4.
大体时间：Up to 4 days after surgery.
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Cognitive function will be assessed with the Montreal Cognitive Assessment (MoCA; scores range from 0 to 30, with higher scores indicating better function) before surgery and on postoperative day 4 or at hospital discharge, whichever occurs first. Delayed neurocognitive recovery (dNCR) is defined as a decline from baseline of >1 SD in MoCA score. |
Up to 4 days after surgery.
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
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Incidence of postoperative delirium within 3 days after surgery.
大体时间：Up to 3 days after surgery.
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Delirium will be assessed twice daily during the first 3 postoperative days using the 3-minute Diagnostic Interview for Confusion Assessment Method (3D-CAM) in non-intubated patients and the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) in intubated patients. |
Up to 3 days after surgery.
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Incidence of delayed neurocognitive recovery (dNCR) on postoperative day 30.
大体时间：At 30 days after surgery.
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Cognitive function will be assessed with the Telephone Montreal Cognitive Assessment (T-MoCA; scores range from 0 to 22, with higher scores indicating better function) before surgery and on postoperative day 30. Delayed neurocognitive recovery (dNCR) is defined as a decline from baseline of >1 SD in T-MoCA score. |
At 30 days after surgery.
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合作者和调查者
调查人员
- 首席研究员：Dong-Xin Wang, MD, PhD、Peking University First Hospital
出版物和有用的链接
一般刊物
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研究记录日期
研究主要日期
学习开始 (估计的)
初级完成 (估计的)
研究完成 (估计的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (实际的)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
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