We appreciate the comments from Zhang et al.1 on our recent article “Delirium in Older Patients after Combined Epidural–General Anesthesia or General Anesthesia for Major Surgery: A Randomized Trial.”2
Consistent with many others,3 our study also found that intraoperative hypotension occurred more frequently in patients given combined epidural–general anesthesia. Increasing evidence suggests that intraoperative hypotension is associated with an increased risk of postoperative delirium.4,5 According to the suggestion of Zhang et al.,1 we included intraoperative hypotension in a post hoc treatment-by-covariate interaction analysis for the primary outcome. Our results did not find significant interaction between treatment intervention and intraoperative hypotension. The effect of combined epidural–general anesthesia on delirium was similar in the subgroups with or without intraoperative hypotension (with intraoperative hypotension [systolic blood pressure < 80 mmHg]: relative risk 0.68; 95% CI, 0.20 to 2.37; without intraoperative hypotension: 0.33, 0.16 to 0.67; interaction P = 0.243).
In our study, delirium was assessed twice daily with the Confusion Assessment Method for the Intensive Care Unit during the first 7 postoperative days. Immediately before assessing delirium, sedation or agitation was assessed with the Richmond Agitation-Sedation Scale. Patients who developed delirium were classified into three subtypes according to the Richmond Agitation-Sedation Scale assessment results. Hyperactive delirium was defined when the Richmond Agitation-Sedation Scale score was consistently positive (from +1 to +4). Hypoactive delirium was defined when the Richmond Agitation-Sedation Scale score was consistently negative or neutral (from –3 to 0). Mixed-type delirium was defined when both hyperactive and hypoactive episodes existed.6 In accord with the results of others, hypoactive delirium was the most common subtype in our patients of the two groups.2
Among our patients, 58 (3.4%) developed delirium within the first 7 postoperative days; of those who developed delirium, 21 (36%) had two episodes or more. The duration of delirium (number of days with at least one episode of delirium) was shorter in patients given combined epidural–general anesthesia (median 0 days [interquartile range, 0 to 0] with combined epidural-general anesthesia vs. 0 days [0 to 0] with general anesthesia alone; mean difference –0.04, 95% CI, –0.08 to –0.01; P < 0.001). Among 58 patients who developed delirium, the duration of delirium did not differ between the two groups (median 1 day [interquartile range, 1 to 2] vs. 1 day [1 to 2]; mean difference 0.42, 95% CI, –0.26 to 1.10; P = 0.546).
This work was funded by the Peking University (Beijing, China) Clinical Research Program [PUCRP201101]. The funder had no role in the study design, data collection, data analysis, data interpretation, or writing of the report.
The authors declare no competing interests.