A 2026 randomized clinical trial published in Anesthesia & Analgesia offers compelling evidence that dexmedetomidine, a sedative with unique neuroprotective properties, significantly reduces the risk of postoperative delirium, cognitive dysfunction, and sleep disturbances in elderly patients following major orthopedic surgery under regional anesthesia.

Key findings at a glance

• Dexmedetomidine reduced:
  
  • Postoperative delirium (POD) from 38.4% to 4.8%
    
  • Emergence delirium (ED) from 38.4% to 2.4%
    
  • Early postoperative cognitive dysfunction (POCD) from 56.4% to 2.4%
    
• Improved sleep quality (lower PSQI scores)
  
• Reduced long-term neuropathic pain (PainDETECT score: 2.4 vs. 5.3)
  
• Greater cognitive stability over 3 months
  

What is dexmedetomidine?

Dexmedetomidine is a selective α2-adrenergic receptor agonist used for sedation. Unlike propofol, it:

• Mimics natural sleep by acting on the preoptic hypothalamic area
  
• Is non-respiratory depressant, preserving normal breathing
  
• Has anti-inflammatory and neuroprotective effects

Study design highlights

Participants:

• 80 elderly patients (aged > 65) undergoing elective hip or knee replacement
  
• All surgeries used regional anesthesia only (no general anesthesia)
  

Groups:

• 41 patients received dexmedetomidine
  
• 39 received propofol
  

Assessment tools:

• POD: Confusion Assessment Method (CAM)
• ED: Riker Sedation-Agitation Scale
• POCD: European Psychometric Battery
• Sleep: Pittsburgh Sleep Quality Index (PSQI)
• Pain: PainDETECT tool

Timeline:

• Assessments were made preoperatively, 48–72 hours post-op, and 3 months post-op
  

Measurable cognitive and neurological benefits

Performance on cognitive tests:

Dexmedetomidine patients maintained stable or improved performance in:

• Visual Verbal Learning Test (VLT) – better memory recall
  
• Concept Shifting Test (CST) – improved cognitive flexibility
  
• Stroop Color Word Test (SCW) – less interference effect
  
• Letter Digit Coding (LDC) – stable processing speed
  
• Propofol patients, in contrast, showed sharp declines in all measures within 48 hours after surgery.

Better sleep quality—short and long term

According to the PSQI results:

• Dexmedetomidine group: Sleep quality improved post-op and remained better at 3 months
  
• Propofol group: Experienced worsened sleep immediately post-op with only partial recovery later
  

Main improvements were in:

• Sleep duration
  
• Time to fall asleep
  
• Reduced nighttime awakenings

Pain outcomes: long-term relief with dexmedetomidine

Although acute postoperative pain scores were only slightly lower, dexmedetomidine patients reported:

• Less severe chronic pain at 3 months
  
• Lower neuropathic pain scores (PainDETECT score: 2.4 vs. 5.3, P = .023)
  
• Men in the propofol group were especially prone to chronic pain

Conclusion: a case for routine dexmedetomidine use?

This study marks a significant shift in perioperative care for elderly orthopedic patients. The neuroprotective, sleep-stabilizing, and pain-reducing benefits of dexmedetomidine present a compelling case for its preferential use over propofol in similar surgical contexts.

What it means for practice:

• Anesthesiologists may consider dexmedetomidine as a first-line sedative for elderly patients under regional blocks.
  
• Surgeons may expect improved cognitive outcomes and fewer complications post-op.
  
• Patients benefit from a clearer mind, better sleep, and less chronic pain.
  

Further large-scale, multicenter studies are warranted to reinforce these findings and establish broader clinical guidelines.

Reference: Karageorgos V et al. A Randomized Clinical Trial of Dexmedetomidine on Delirium, Cognitive Dysfunction, and Sleep After Non-Ambulatory Orthopedic Surgery With Regional Anesthesia. Anesth Analg. 2026;142:102-113.

Read more about this study in NYSORA’s Anesthesia Assistant App.