MInimizing Delirium With Nasal Dexmedetomidine-InducEd Sleep (MIDDIES)

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.

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.

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