Randomized Controlled Trial
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Jul 26, 2021; 9(21): 5909-5920
Published online Jul 26, 2021. doi: 10.12998/wjcc.v9.i21.5909
Effects of perioperative rosuvastatin on postoperative delirium in elderly patients: A randomized, double-blind, and placebo-controlled trial
Xiao-Qin Xu, Jing-Zhi Luo, Xiao-Yu Li, Hai-Qin Tang, Wei-Hong Lu
Xiao-Qin Xu, Jing-Zhi Luo, Xiao-Yu Li, Hai-Qin Tang, Wei-Hong Lu, Department of Anesthesiology, Wuxi Clinical College of Anhui Medical University, 904th Hospital of Joint Logistic Support Force of PLA, Wuxi Clinical College of Anhui Medical University, Wuxi 214044, Jiangsu Province, China
Author contributions: Xu XQ, Li XY, and Luo JZ designed the study and analyzed the data; Tang HQ, Lu WH, and Luo JZ collected the data; Xu XQ and Li XY interpreted the data; Xu XQ, Li XY, Tang HQ, Lu WH, and Luo JZ prepared the manuscript; all authors have read and approved the manuscript.
Institutional review board statement: The study protocol was approved by the Clinical Research Ethics Committees of Anhui Medical University Affiliated with Wuxi Clinical College (ChiCTR-IPR-17011984 and YXLL-2017-02). The study protocol received Ethics Committee approval from all participating centers. Written informed consent was obtained from patients whose competence was established by their accurate orientation for time, place, and person, as well as an understanding of the recruiter’s description of the trial, or otherwise from their next of kin or their legal representative.
Clinical trial registration statement: Chictr.org.cn, ChiCTR-IPR-17011984 (registration date: 13/07/2017).
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: The authors have no competing interests to declare.
Data sharing statement: The datasets used and analyzed during the current study are available from the corresponding author upon reasonable request.
CONSORT 2010 statement: The authors have read the CONSORT 2010 Statement, and the manuscript was prepared and revised according to the CONSORT 2010 Statement.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Xiao-Yu Li, MM, Chief Nurse, Department of Anesthesiology, Wuxi Clinical College of Anhui Medical University, 904th Hospital of Joint Logistic Support Force of PLA, Wuxi Clinical College of Anhui Medical University, No. 101 Xingyuan North Road, Wuxi 214044, Jiangsu Province, China. 742888988@qq.com
Received: March 30, 2021
Peer-review started: March 30, 2021
First decision: April 28, 2021
Revised: May 4, 2021
Accepted: June 7, 2021
Article in press: June 7, 2021
Published online: July 26, 2021
Abstract
BACKGROUND

Experimental evidence has indicated the benefits of statins for the treatment of postoperative delirium. Previously, clinical trials did not reach definite conclusions on the effects of statins on delirium. Some clinical trials have indicated that statins reduce postoperative delirium and improve outcomes, while some studies have reported negative results.

AIM

To evaluate whether perioperative rosuvastatin treatment reduces the incidence of delirium and improves clinical outcomes.

METHODS

This randomized, double-blind, and placebo-controlled trial was conducted in a single center in Jiangsu, China. This study enrolled patients aged greater than 60 years who received general anesthesia during elective operations and provided informed consent. A computer-generated randomization sequence (in a 1:1 ratio) was used to randomly assign patients to receive either rosuvastatin (40 mg/d) or placebo. Participants, care providers, and investigators were all masked to group assignments. The primary endpoint was the incidence of delirium, which was assessed twice daily with the Confusion Assessment Method during the first 7 postoperative days. Analyses were performed on intention-to-treat and safety populations.

RESULTS

Between January 1, 2017 and January 1, 2020, 3512 patients were assessed. A total of 821 patients were randomly assigned to receive either placebo (n = 411) or rosuvastatin (n = 410). The incidence of postoperative delirium was significantly lower in the rosuvastatin group [23 (5.6%) of 410 patients] than in the placebo group {42 (13.5%) of 411 patients [odds ratios (OR) = 0.522, 95% confidence interval (CI): 0.308-0.885; P < 0.05]}. No significant difference in 30-d all-cause mortality (6.1% vs 8.7%, OR = 0.67, 95%CI: 0.39-1.2, P = 0.147) was observed between the two groups. Rosuvastatin decreased the hospitalization time (13.8 ± 2.5 vs 14.2 ± 2.8, P = 0.03) and hospitalization expenses (9.3 ± 2.5 vs 9.8 ± 2.9, P = 0.007). No significant differences in abnormal liver enzymes (9.0% vs 7.1%, OR = 1.307, 95%CI: 0.787-2.169, P = 0.30) or rhabdomyolysis (0.73% vs 0.24%, OR = 3.020, 95%CI: 0.31-29.2, P = 0.37) were observed between the two groups.

CONCLUSION

The current study suggests that perioperative rosuvastatin treatment reduces the incidence of delirium after an elective operation under general anesthesia. However, the evidence does not reveal that rosuvastatin improves clinical outcomes. The therapy is safe. Further investigation is necessary to fully understand the potential usefulness of rosuvastatin in elderly patients.

Keywords: Perioperative rosuvastatin, Postoperative delirium, Elderly, General anesthesia, Randomised controlled trial

Core Tip: Postoperative delirium is a severe clinical syndrome, which may induce long-term cognitive impairment and death/disability. This randomized, double-blind, and placebo-controlled trial indicated that perioperative rosuvastatin treatment can significantly decrease the incidence of delirium after an elective operation under general anesthesia, and reduce the hospitalization time and hospitalization expenses, but did not improve the clinical outcomes.