Role of peripheral inflammatory markers in postoperative cognitive dysfunction (POCD): a meta-analysis

Linying Peng, Liwei Xu, Wen Ouyang, Linying Peng, Liwei Xu, Wen Ouyang

Abstract

Background: Postoperative cognitive dysfunction (POCD) is common following cardiac and non-cardiac surgery, but the pathogenic mechanisms remain unknown. Many studies suggest that an inflammatory response is a key contributor to POCD. The current meta-analysis shows that the levels of peripheral inflammatory markers are associated with POCD.

Methods: An online search was performed to identify peer-reviewed studies without language restriction that measured peripheral inflammatory markers of patients with and without POCD, using PubMed, ScienceDirect, SinoMed and the National Knowledge Infrastructure database. Extracted data were analyzed with STATA (version 12).The standardized mean difference (SMD) and the 95% confidence interval (95%CI) were calculated for each outcome using a random effect model. Tests of heterogeneity assessment of bias, and meta-regression were performed in the meta-analysis.

Results: A total of 13 studies that measured the concentrations of peripheral inflammatory markers were included. The current meta-analysis found significantly higher concentrations of S-100β(SMD[95%CI]) (1.377 [0.423, 2.331], p-value < 0.001, N [POCD/non-POCD] =178/391, 7 studies), and interleukin(IL)-6 (SMD[95%CI]) (1.614 [0.603,2.624], p-value < 0.001, N[POCD/non-POCD] = 91/99, 5 studies), but not of neuron specific enolase, interleukin-1β, or tumor necrosis factor-α , in POCD compared with patients without POCD. In meta-regression analyses, a significant positive association was found between the SMD and the preoperative interleukin-6 peripheral blood concentration in patients with POCD (Coef.= 0.0587, p-value=0.038, 5 studies).

Conclusions: This study shows that POCD is indeed correlated with the concentrations of peripheral inflammatory markers, particularly interleukin-6 and S-100β.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1. Flow diagram for article selection.
Figure 1. Flow diagram for article selection.
Figure 2. Studies of peripheral blood S-100β.
Figure 2. Studies of peripheral blood S-100β.
Forest plot for S-100β displaying the results of the random effects meta-analysis for the association between peripheral blood S-100β and postoperative cognitive dysfunction (POCD). The standardized mean difference is presented on the horizontal axis; positive values denote higher serum levels in POCD patients; negative values denote higher serum levels in control subjects. The dashed line is at the overall standardized mean difference. CI, confidence interval; SMD, standardized mean difference.
Figure 3. Studies of peripheral blood IL-6.
Figure 3. Studies of peripheral blood IL-6.
Forest plot for IL-6 displaying the results of the random-effects meta-analysis for the association between peripheral blood IL-6 concentrations and POCD. The standardized mean difference is presented on the horizontal axis; positive values denote higher serum levels in patients; negative values denote higher serum levels in control subjects. The dashed line is at the overall weighted mean difference. CI, confidence interval; SMD, standardized mean difference.
Figure 4. Association of preoperative IL-6 blood…
Figure 4. Association of preoperative IL-6 blood concentration in POCD patients with plasma IL-6 SMD using meta-regression.
Plot of the preoperative IL-6 peripheral blood concentration vs. the peripheral blood IL-6 SMD in the 5 included studies showing a fitted random effects meta-regression line.( 5 studies, Coef.=0 .0587 ,p-value = 0.038 ) Coef., coefficient.
Figure 5. Association of preoperative S-100β blood…
Figure 5. Association of preoperative S-100β blood concentration in all subjects with plasma S-100β SMD using meta-regression.
Plot of the preoperative S-100β peripheral blood concentration vs. the peripheral blood S-100β SMD in the 6 included studies, showing a random effects meta-regression line. (6 studies, Coef.= 9.554,p-value = 0.290 ) Coef., coefficient.

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