Intranasal Dexmedetomidine, Major Abdominal Surgery, Postoperative Delirium (POD), Sleep Disturbances
Conditions
Keywords
dexmedetomidine, intranasal administration
Brief summary
This study aims to determine whether, compared with placebo, the nighttime self-administration of a nasal dexmedetomidine is effective at inducing sleep and preventing postoperative delirium in high-risk patients.
Detailed description
Delirium is an acute, short-term brain dysfunction characterized by fluctuating consciousness, cognitive decline, inattention, and sleep-wake cycle disruption. Postoperative delirium (POD), occurring predominantly within the first postoperative week (especially days 3-5 in elderly patients), affects 11-45% of older adults after major surgery. POD prolongs hospitalization, increases morbidity and mortality 5,65,6, yet its pathophysiology remains unclear, and evidence-based pharmacological prevention is lacking. Thus, effective POD prevention strategies are urgently needed. Preoperative anxiety, a modifiable risk factor for POD, affects 11-80% of surgical patients. It contributes to sleep disturbances (e.g., insomnia, early awakening), which may exacerbate POD via neuroendocrine and immune dysregulation. However, benzodiazepines (e.g., lorazepam, diazepam, midazolam), though effective anxiolytics, increase delirium risk and are contraindicated preoperatively per current guidelines. Dexmedetomidine (DEX), a selective α2-adrenoceptor agonist, induces physiological non-REM sleep without respiratory depression or hemodynamic instability. Its nasal formulation offers high bioavailability (82%), ease of administration, and is approved in China for preoperative sedation/anxiety. While intravenous (IV) DEX reduces POD in predominant ICU settings, its use in general wards remains unexplored. Preclinical studies suggest DEX enhances glymphatic clearance and exerts anti-inflammatory effects, potentially mitigating the development of POD. This study thus hypothesize that a nasal dexmedetomidine is effective at inducing sleep and preventing postoperative delirium in high-risk patient population. We set to demonstrate that to determine whether, compared with placebo, the nighttime self-administration of a nasal dexmedetomidine is effective at inducing sleep and preventing postoperative delirium in older patients undergoing major abdominal surgery.
Interventions
DRUGDexmedetomidine
Intranasal dexmedetomidine (100 µg total: 4 sprays, 25 µg/spray; Hengrui Medicine, China) self-administered preoperatively (\~9 PM) and optionally on the night of surgery (patient decides dose: 0, 2 sprays, or 4 sprays).
DRUGPlacebo
Intranasal water for injection (4 sprays, identical volume as nasal dexmedetomidine; Hengrui Medicine, China) self-administered preoperatively (\~9 PM) and optionally on the night of surgery (patient decides dose: 0, 2 sprays, or 4 sprays).
Sponsors
Sixth Affiliated Hospital, Sun Yat-sen University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
65 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
* Aged 65-90 years * Scheduled for a major abdominal surgery with estimated surgery time ≥ 2 hours
Exclusion criteria
* Blind, deafness or the inability to speak mandarin * Allergy to dexmedetomidine. * Renal and liver failure requiring dialysis or Child-Pugh score \> 5 * Follow-up difficulties (i.e. active substance abuse, psychotic disorder, homelessness) * Previous major abdominal or cardiac surgery within 1 year of surgical procedure * Chronic therapy with benzodiazepines and/or antipsychotics. Severe deficit due to structural or anoxic brain damage * Body weight \< 35 kg
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of postoperative delirium | Up to postoperative day (POD) 7 or discharge (whichever first). | Confusion Assessment Method |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Delirium severity | Up to postoperative day (POD) 7 or discharge (whichever first) | Confusion Assessment Method Score |
| Physical activity | Up to postoperative day (POD) 3 | Fitbit Flex2 tracker |
| Sleep quality | Up to postoperative day (POD) 3 | Fitbit Flex2 tracker and Athens Insomnia Scale |
| Anxiety | Up to postoperative day (POD) 3 | Hamilton Anxiety Scale |
| Pain intensity | Up to postoperative day (POD) 3 | Numerical Rating Scale |
| Opioid consumption | Up to postoperative day (POD) 3 | Intravenous morphine equivalents |
| Health related quality of life | On postoperative day (POD) 3 and 30 | Health related quality of life assessed with the SF-36 health survey |
| Quality of Recovery | Up to postoperative day (POD) 3 | The Quality of Recovery-15 questionnaire |
| Postoperative Nausea and Vomiting | Up to postoperative day (POD) 3 | Postoperative Nausea and Vomiting Scale |
| Post-anesthesia Care Unit (PACU) length of stay | Up to postoperative day (POD) 1 | Post-anesthesia Care Unit (PACU) length of stay |
Contacts
CONTACTMentying Ding, MD.
Outcome results
None listed