Reproducing an earlier pilot trial, Sieber and colleagues randomized 200 patients to receive light vs deep propofol sedation while undergoing a repair of hip fractures under spinal anesthesia and concluded that there was no statistically significant association between the assignment to deep sedation and postoperative delirium. This result is disappointing, but it is consistent with the interpretation that most delirium risk is due to unmodifiable factors like comorbid disease, “evil humors” that are released by trauma and/or surgery, and an underlying cognitive pathology that may or may not be detectible on preoperative testing results. Because the authors were statistically challenged by a slightly lower rate of postoperative delirium than their pilot trial had indicated² and because there was substantially less separation between the light and deep sedation groups than the trial’s power calculations had required, it is easy to understand why the article’s Discussion focuses heavily on the prespecified subgroup analysis, the Charlson comorbidity index (CCI) of 0 patients.

There is a larger question than preventing postoperative delirium at stake here. The association between delirium and dementia is well documented in observational studies. Although the language around delirium and subsequent dementia is taking on an increasingly causal tone,³ this is probably inappropriate given the potential for the confounding of observational data in a syndrome with incompletely understood, and intersecting, underlying pathologic mechanisms. The key to understanding the association of delirium with dementia is a well-powered randomized clinical trial of a therapy that effectively reduces postoperative delirium. Unfortunately, the trial conducted by Sieber et al¹ is not that; the small sample size in the CCI score of 0 subgroup (notably, there was only an imbalance of 3 patients with delirium between the light and heavy sedation groups in this group) means that this finding is highly vulnerable to chance. While we can have cautious enthusiasm for this suggested way to reduce postoperative delirium, we must regard these findings with an appropriate degree of skepticism that is proportional to the uncertainty of placing full confidence in a 72-patient subgroup analysis.

Despite its limitations, Sieber and colleagues have produced thoughtful, unconfounded data on one of many unanswered questions in the study of perioperative delirium: does higher-dose propofol sedation contribute to postoperative delirium? The answer remains maybe.