Effect of Midazolam on Postoperative Delirium: Comment
Letter to the Editor Summary
Authors: Christy Khoudrietchan et al.
Source: Anesthesiology. January 2026 issue.
Summary:
This Letter to the Editor responds to Li et al.’s study evaluating whether intraoperative midazolam increases postoperative delirium in elderly surgical patients. The authors commend the original investigators but raise several methodological concerns that may affect interpretation of the findings.
They note that the primary endpoint—delirium within seven days—was measured using the 3D-CAM twice daily. Because delirium can fluctuate rapidly throughout the day, the authors argue that assessing only every 12 hours risks missing episodes, particularly during the first 24–72 hours after surgery when delirium is most common. Increasing assessment frequency would catch more cases, but could strain staffing or interrupt patient sleep.
They also highlight that most delirium cases in the original study occurred on postoperative day 1, with the average onset around midday. This pattern strengthens the argument that infrequent assessments risk under-detection.
Another major concern is confounding. The authors point out that the original paper did not specify whether patients received other sedatives that could influence delirium risk. They also observe that patients given midazolam tended to be younger and healthier. Because healthier patients are generally less likely to develop delirium, this imbalance could bias the results. Statistical methods such as inverse probability weighting or matching could have helped address this.
The authors additionally comment on a secondary endpoint: postoperative anxiety. A small decrease in anxiety was noted among patients who did not receive midazolam. Although statistically significant, they caution that this was an exploratory outcome and may reflect chance findings. They also note that the anxiety scale used (GAD-7) is not validated as a postoperative measure, limiting interpretation.
Overall, the letter supports the importance of the original study but urges caution in interpreting the magnitude of the midazolam–delirium relationship due to potential under-detection, confounding, and limitations of secondary outcomes.
What You Should Know
• Twice-daily delirium checks may miss cases because delirium fluctuates hour to hour.
• Most delirium occurred on postoperative day 1, reinforcing the need for high-frequency early assessments.
• Differences in baseline health and age between groups may have biased results.
• Exploratory findings regarding postoperative anxiety should be interpreted cautiously.
• The authors support the study concept but emphasize that methodological issues limit firm conclusions.