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.
Studieoversigt
Status
Betingelser
Intervention / Behandling
Detaljeret beskrivelse
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.
Undersøgelsestype
Tilmelding (Anslået)
Fase
- Fase 4
Kontakter og lokationer
Studiekontakt
- Navn: Dong-Xin Wang, MD, PhD
- Telefonnummer: 86 10 83572784
- E-mail: wangdongxin@hotmail.com
Undersøgelse Kontakt Backup
- Navn: Huai-Jin Li, MD
- Telefonnummer: 86 10 83572460
- E-mail: sophie.lee.coffee@gmail.com
Studiesteder
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Beijing Municipality
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Beijing, Beijing Municipality, Kina, 100034
- Peking University First Hospital
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Kontakt:
- Huai-Jin Li, MD
- Telefonnummer: +8613488659162
- E-mail: sophie.lee.coffee@gmail.com
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Deltagelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Køn, der er berettiget til at studere
Beskrivelse
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.
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Forebyggelse
- Tildeling: Randomiseret
- Interventionel model: Parallel tildeling
- Maskning: Firedobbelt
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
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Eksperimentel: 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.
Andre navne:
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Placebo komparator: 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.
Andre navne:
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Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
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Incidence of delayed neurocognitive recovery (dNCR) on postoperative day 4.
Tidsramme: 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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Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
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Incidence of postoperative delirium within 3 days after surgery.
Tidsramme: 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.
Tidsramme: 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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Samarbejdspartnere og efterforskere
Sponsor
Efterforskere
- Ledende efterforsker: Dong-Xin Wang, MD, PhD, Peking University First Hospital
Publikationer og nyttige links
Generelle publikationer
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- Schwenk ES, Viscusi ER, Buvanendran A, Hurley RW, Wasan AD, Narouze S, Bhatia A, Davis FN, Hooten WM, Cohen SP. Consensus Guidelines on the Use of Intravenous Ketamine Infusions for Acute Pain Management From the American Society of Regional Anesthesia and Pain Medicine, the American Academy of Pain Medicine, and the American Society of Anesthesiologists. Reg Anesth Pain Med. 2018 Jul;43(5):456-466. doi: 10.1097/AAP.0000000000000806.
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- 2026R0664
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