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Preoperative Salivary Cortisol AM/PM Ratio Predicts Early Postoperative Cognitive Dysfunction After Noncardiac Surgery in Elderly Patients

Han, Yuan, MD, PhD*,†; Han, Liu, MD*; Dong, Meng-Meng, MD*; Sun, Qing-Chun, MD*; Zhang, Zhen-Feng, MD*; Ding, Ke, MD*; Zhang, Yao-Dong, MD†,‡; Mannan, Abdul, MD*,†; Xu, Yi-Fan, MD; Ou-Yang, Chang-Li, MD§; Li, Zhi-Yong, MD; Gao, Can, MD, PhD; Cao, Jun-Li, MD, PhD*,†

doi: 10.1213/ANE.0000000000003740
Geriatric Anesthesia: Original Clinical Research Report

BACKGROUND: The diagnosis of postoperative cognitive dysfunction (POCD) requires complicated neuropsychological testing and is often delayed. Possible biomarkers for early detection or prediction are essential for the prevention and treatment of POCD. Preoperative screening of salivary cortisol levels may help to identify patients at elevated risk for POCD.

METHODS: One hundred twenty patients >60 years of age and undergoing major noncardiac surgery underwent neuropsychological testing 1 day before and 1 week after surgery. Saliva samples were collected in the morning and the evening 1 day before surgery. POCD was defined as a Z-score of ≤−1.96 on at least 2 different tests. The primary outcome was the presence of POCD. The primary objective of this study was to assess the relationship between the ratio of AM (morning) to PM (evening) salivary cortisol levels and the presence of POCD. The secondary objective was to assess the relationship between POCD and salivary cortisol absolute values in the morning or in the evening.

RESULTS: POCD was observed in 17.02% (16 of 94; 95% confidence interval [CI], 9.28%–24.76%) of patients 1 week after the operation. A higher preoperative AM/PM salivary cortisol ratio predicted early POCD onset (odds ratio [OR], 1.56; 95% CI, 1.20–2.02; P = .001), even after adjusting for the Mini-Mental Sate Examination score (odds ratio, 1.55; 95% CI, 1.19–2.02; P = .001). The area under the receiver operating characteristic curve for the salivary cortisol AM/PM ratio in individuals with POCD was 0.72 (95% CI, 0.56–0.88; P = .006). The optimal cutoff value was 5.69, with a sensitivity of 50% and specificity of 91%.

CONCLUSIONS: The preoperative salivary cortisol AM/PM ratio was significantly associated with the presence of early POCD. This biomarker may have potential utility for screening patients for an increased risk and also for further elucidating the etiology of POCD.

From the *Department of Anesthesiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou City, Jiangsu Province, China

Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Yunlong District, Xuzhou City, Jiangsu Province, China

School of Public Health, Xuzhou Medical University, Yunlong District, Xuzhou City, Jiangsu Province, China

§Department of Nuclear Medicine, The Affiliated Hospital of Xuzhou Medical University, Quanshan District, Xuzhou City, Jiangsu Province, China.

Published ahead of print 18 July 2018.

Accepted for publication July 18, 2018.

Funding: Supported by the National Natural Science Foundation of China (81720108013, 81571059); Jiangsu Provincial Special Program of Medical Science (BL2014029); Scientific Research Innovation Project for Graduate Students of Jiangsu Universities, Jiangsu, China (SJZZ16_0290); and China Postdoctoral Science Foundation Funded Project (Project No: 2015M580473).

The authors declare no conflicts of interest.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website.

Y. Han, L. Han, and M.-M. Dong contributed equally to this work and share first authorship.

Reprints will not be available from the authors.

Address correspondence to Jun-Li Cao, MD, PhD, Department of Anesthesiology, The Affiliated Hospital of Xuzhou Medical University, No. 99 Huaihai Rd, Quanshan District, Xuzhou City 221002, Jiangsu Province, China. Address e-mail to

© 2019 International Anesthesia Research Society
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