Authors: Zuylen ML van et al.
Anesthesia & Analgesia, 2026 (Letter to the Editor)
This Letter to the Editor critiques a recent randomized trial evaluating dexmedetomidine infusion during lower-limb orthopedic surgery under regional anesthesia and its reported reductions in postoperative delirium (POD), postoperative cognitive dysfunction (POCD), and improvements in sleep and pain outcomes.
The author raises several methodological and interpretive concerns, arguing that while the findings are intriguing, the conclusions may be overstated.
Key Concerns Raised
-
Definition and timing of POCD
The letter questions the use of the term POCD in the immediate postoperative period. International consensus statements recommend assessing cognitive dysfunction at least 30 days postoperatively using validated methodology. Early postoperative cognitive changes are often influenced by residual sedatives, analgesics, or delirium rather than representing true long-term cognitive dysfunction. -
Neuropsychological assessment limitations
The critique notes potential methodological limitations in cognitive testing, including reliability of indices and possibly using abbreviated or less robust instruments. The unusually large effect sizes—such as a reported 23-fold increased incidence of POCD with propofol compared to dexmedetomidine—are considered implausibly high and inconsistent with prior literature. -
Unexpectedly high delirium rates
The incidence of postoperative delirium in the propofol group (38%) is described as higher than expected compared to prior studies, raising concern for unmeasured confounding or sampling variability. -
Sleep quality measurement
Both groups received similar anesthesia and regional techniques, yet sleep improved only in the dexmedetomidine group. The author questions whether crude sleep assessment tools can meaningfully evaluate sleep architecture. More precise measures (e.g., polysomnography) would be required to make mechanistic conclusions. -
Overextension of conclusions
While dexmedetomidine may influence sedation depth and sleep patterns, the study was not powered to assess independent effects apart from sedation level. Thus, conclusions linking dexmedetomidine directly to sustained neurocognitive improvements may exceed the data’s strength.
Central Thesis
The letter emphasizes that sleep and cognition are complex, multifactorial processes. Drawing firm conclusions about long-term neurocognitive protection from limited early postoperative data may be premature. The findings are better interpreted as exploratory rather than definitive.
Key Points
• Early cognitive changes should not automatically be labeled POCD without standardized 30-day assessment.
• Extremely large effect sizes raise concerns about methodological limitations or confounding.
• Sleep outcomes require more precise measurement to support mechanistic claims.
• Delirium incidence reported in the control group appears unusually high.
• Findings should be considered hypothesis-generating rather than practice-changing.
What You Should Know
This letter reinforces a broader caution in perioperative neurocognitive research: early postoperative testing is vulnerable to confounding by sedation depth, residual anesthetics, analgesics, and acute delirium.
For clinicians and researchers, it highlights the importance of:
• Clear terminology (delirium vs early cognitive change vs POCD)
• Appropriate timing of testing
• Adequate study power
• Avoiding overinterpretation of large relative differences
In neurocognitive anesthesia research, methodological rigor and long-term follow-up remain essential before altering routine practice.
Thank you to Anesthesia & Analgesia for allowing us to summarize and share this letter.