Effect of dexmedetomidine on postoperative cognitive dysfunction and inflammation in patients after general anaesthesia: A PRISMA-compliant systematic review and meta-analysis

Wan Yang, Ling-Suo Kong, Xing-Xing Zhu, Rui-Xiang Wang, Ying Liu, Lan-Ren Chen, Wan Yang, Ling-Suo Kong, Xing-Xing Zhu, Rui-Xiang Wang, Ying Liu, Lan-Ren Chen

Abstract

Background: Neuroprotective effects of dexmedetomidine are reported in preclinical and clinical studies but evidence regarding the postoperative neurocognitive function is still unclear. This study performed a meta-analysis on outcomes of studies which examined neurocognitive performance and inflammatory factors to investigate the effects of dexmedetomidine on postoperative cognitive dysfunction (POCD) and inflammation in patients after general anaesthesia.

Methods: Literatures were searched in several electronic databases and studies were selected by following precise inclusion criteria. We searched PubMed, EMBASE, the Cochrane Library, China Academic Journals full-text database (CNKI), and Google Scholar to find randomized controlled trials (RCTs) of the influence of dexmedetomidine on POCD and inflammation in patients who had undergone general anaesthesia. Two researchers independently screened the literature, extracted data, and evaluated quality of methodology against inclusion and exclusion criteria. Meta-analyses of pooled ORs of POCD incidences and mean differences in neurocognitive assessment scores and inflammation levels were carried out and subgroup analyses were performed. Stata 12.0 was used to conduct our meta-analysis.

Results: Twenty-six RCTs were included. Compared with controls, perioperative dexmedetomidine treatment significantly reduced the incidence of POCD (pooled ORs = 0.59, 95% confidence interval (CI) 0.45-2.95) and improved Mini-Mental State Examination (MMSE) score (standardized mean difference (SMD) = 1.74, 95% CI 0.43-3.05) on the first postoperative day. Furthermore, perioperative dexmedetomidine treatment significantly decreased IL-6 (SMD = -1.31, 95% CI -1.87-0.75, P < .001) and TNF-α (SMD = -2.14, 95% CI -3.14-1.14, P < .001) compared to saline/comparators treatment. In the stratified analysis by surgical type, age, type of control, and study region, the differences were also significant between dexmedetomidine- and saline-treated patients.

Conclusion: Perioperative dexmedetomidine treatment is associated with significantly reduced incidence of POCD and inflammation and better neurocognitive function postoperatively in comparison with both saline controls and comparator anaesthetics.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Figure 1
Figure 1
Flowchart of the literature search.
Figure 2
Figure 2
Effect of dexmedetomidine treatment on MMSE score in patients with general anaesthesia. Forest plot of mean difference analyzed in random-effect model at 95% confidence intervals (CI). MMSE = Mini-Mental State Examination.
Figure 3
Figure 3
Prevention of POCD by dexmedetomidine in patients compared to controls on first, third, and seventh day. Forest plot of odds ratio, analyzed by Mantel–Haenszel statistics in the random-effect model. Meta-analysis of the relationship on first day (Fig. 3a), third day (Fig. 3b) and seventh day (Fig. 3c), respectively. POCD = postoperative cognitive dysfunction.
Figure 4
Figure 4
Reduction of inflammation by dexmedetomidine in patients compared to controls. Forest plot of odds ratio, analyzed by Mantel–Haenszel statistics in the random-effect model. Meta-analysis of the effect on TNF-α (Fig. 4a) and IL-6 (Fig. 4b), respectively.
Figure 5
Figure 5
Funnel plot of studies that examined the association between dexmedetomidine treatment and MMSE score. MMSE = Mini-Mental State Examination.

References

    1. Hood R, Budd A, Sorond FA, et al. Peri-operative neurological complications. Anaesthesia 2018;73Suppl 1:67–75.
    1. Hermanides J, Qeva E, Preckel B, et al. Perioperative hyperglycaemia and neurocognitive outcome after surgery: a systematic review. Minerva Anestesiol 2018;84:1178–88.
    1. Wang B, Li S, Cao X, et al. Blood-brain barrier disruption leads to postoperative cognitive dysfunction. Curr Neurovasc Res 2017;14:359–67.
    1. Steinthorsdottir KJ, Kehlet H, Aasvang EK. Surgical stress response and the potential role of preoperative glucocorticoids on post-anesthesia care unit recovery. Minerva Anestesiol 2017;83:1324–31.
    1. Feinkohl I, Winterer G, Spies CD, et al. Cognitive reserve and the risk of postoperative cognitive dysfunction. Dtsch Arztebl Int 2017;114:110–7.
    1. Vide S, Gambús PL. Tools to screen and measure cognitive impairment after surgery and anesthesia. Presse Med 2018;47(4 Pt 2):e65–72.
    1. Winterer G, Androsova G, Bender O, et al. Personalized risk prediction of postoperative cognitive impairment - rationale for the EU-funded BioCog project. Eur Psychiatry 2018;50:34–9.
    1. Benhamou D, Brouquet A. Postoperative cerebral dysfunction in the elderly: diagnosis and prophylaxis. J Visc Surg 2016;153(6S):S27–32.
    1. Shutes BL, Gee SW, Sargel CL, et al. Dexmedetomidine as single continuous sedative during noninvasive ventilation: typical usage, hemodynamic effects, and withdrawal. Pediatr Crit Care Med 2018;19:287–97.
    1. Ray T, Tobias JD. Dexmedetomidine for sedation during electroencephalographic analysis in children with autism, pervasive developmental disorders, and seizure disorders. J Clin Anesth 2008;20:364–8.
    1. Wu J, Vogel T, Gao X, et al. Neuroprotective effect of dexmedetomidine in a murine model of traumatic brain injury. Sci Rep 2018;8:4935.
    1. Hu J, Vacas S, Feng X, et al. Dexmedetomidine prevents cognitive decline by enhancing resolution of high mobility group box 1 protein-induced inflammation through a vagomimetic action in mice. Anesthesiology 2018;128:921–31.
    1. Li Y, He R, Chen S, et al. Effect of dexmedetomidine on early postoperative cognitive dysfunction and peri-operative inflammation in elderly patients undergoing laparoscopic cholecystectomy. Exp Ther Med 2015;10:1635–42.
    1. Chen W, Liu B, Zhang F, et al. The effects of dexmedetomidine on post-operative cognitive dysfunction and inflammatory factors in senile patients. Int J Clin Exp Med 2015;8:4601–5.
    1. Ding L, Zhang H, Mi W, et al. Effects of dexmedetomidine on anesthesia recovery period and postoperative cognitive function of patients after robot-assisted laparoscopic radical cystectomy. Int J Clin Exp Med 2015;8:11388–95.
    1. Liu Y, Ma L, Gao M, et al. Dexmedetomidine reduces postoperative delirium after joint replacement in elderly patients with mild cognitive impairment. Aging Clin Exp Res 2016;28:729–36.
    1. Zhang Y, Xing Z, Xu Y, et al. Effects of different doses of dexmedetomidine on cognitive dysfunction in elderly patients early after laparoscopic surgery for colorectal cancer. Nan Fang Yi Ke Da Xue Xue Bao 2014;34:743–6.
    1. Lu J, Chen G, Zhou H, et al. Effect of parecoxib sodium pretreatment combined with dexmedetomidine on early postoperative cognitive dysfunction in elderly patients after shoulder arthroscopy: a randomized double blinded controlled trial. J Clin Anesth 2017;41:30–4.
    1. Meng Y, Zhang H, Yu H. Effect of dexmedetomidine on cerebral oxygen saturation and cognitive function in elder patients afterlaparoscopic surgery. J Tianjin Med Univ 2016;22:66–8.
    1. Guan Y, Chen Y, Su S, et al. Influence of subanesthetic dose ketamine and loading dose dexmedetomidineon postoperative cognitive dysfunction in the elderly patients. China Med Herald 2015;12:61–3.
    1. Wang Z, Chen Q, Guo H, et al. Effects of dexmedetomidine on H-FABP, CK-MB, cTnI levels, neurological function and near-term prognosis in patients undergoing heart valve replacement. Exp Ther Med 2017;14:5851–6.
    1. Liu Y, Wan X, Liu M, et al. Influence of dexmedetomidineon postoperative cognitive dysfunction in the elderly patients. Herald Med 2015;34:214–7.
    1. Xu G, Li LL, Sun ZT, et al. Effects of dexmedetomidine on postoperative cognitive dysfunction and serum levels of b-amyloid and neuronal microtubule-associated protein in orthotopic liver transplantation patients. Ann Transplant 2016;21:508–15.
    1. Li Y, Dai H. Effect of dexmedetomidineon postoperative cognitive dysfunction in the elderly patients receiving abdominal operation in general anesthesia. J Clin Anesthesiol 2014;30:964–7.
    1. Wang K, Li C, Shi J, et al. Effects of patient-controlled intravenous analgesia with dexmedetomidine and sufentanil on postoperative cognition in elderly patients after spine surgery. Zhonghua Yi Xue Za Zhi 2015;95:2437–41.
    1. Chen J, Yan J, Han X. Dexmedetomidine may benefit cognitive function after laparoscopic cholecystectomy in elderly patients. Exp Ther Med 2013;5:489–94.
    1. Jia ZM, Hao HN, Huang ML, et al. Influence of dexmedetomidine to cognitive function during recovery period for children with general anesthesia. Eur Rev Med Pharmacol Sci 2017;21:1106–11.
    1. Peng Z, Zhang W, Chu Q. Effect of dexmedetomidineon early postoperative cognitive function after transurethrue resection of prostate in elderly patients. J Clin Anesthesiol 2013;29:945–7.
    1. Deiner S, Luo X, Lin HM, et al. Intraoperative infusion of dexmedetomidine for prevention of postoperative delirium and cognitive dysfunction in elderly patients undergoing major elective noncardiac surgery: a randomized clinical trial. JAMA Surg 2017;152:e171505.
    1. Zhang X, Piao M, Wang Y, et al. Influence of sub-anesthetic dose of ketamine and dexmedetomidine on early postoperative cognitive function in elderly orthopedic patients under total intravenous anesthesia. J Jilin Univ 2013;39:133–7.
    1. Ma XD, Li BP, Wang DL, et al. Postoperative benefits of dexmedetomidine combined with flurbiprofenaxetil after thyroid surgery. Exp Ther Med 2017;14:2148–52.
    1. Guo Y, Sun L, Zhang J, et al. Preventive effects of low-dose dexmedetomidine on postoperative cognitive function and recovery quality in elderly oral cancer patients. Int J Clin Exp Med 2015;8:16183–90.
    1. Xu HY, Fu GH, Wu GS. Effect of dexmedetomidine-induced anesthesia on the postoperative cognitive function of elder patients after laparoscopic ovarian cystectomy. Saudi J Biol Sci 2017;24:1771–5.
    1. Bo P, Yan D, Shui C. Influence of dexmedetomidine on the postoperative cognitive function under surgery in elder patients. Chongqing Yixue 2013;42:2107–9.
    1. Kong L, Zhang Y, Lu X. Effect of dexmedetomidineon perioperative cerebral oxygen metabolism and postoperative cognitive function in elderly patients undergoing stomach cancer surgery. China J Modern Med 2018;28:52–6.
    1. Liu J, Wang J, Zhang R, et al. Effect of dexmedetomidineon postoperative cognitive function in patients with obstructive sleep apnea. J Pract Med 2017;33:1479–82.
    1. Xu Y, Song Y, Xu F. Dexmedetomidine effects on hemodynamic changes and cognitive ability of elderly patients undergoing lumbar surgery. Chin J Tissue Eng Res 2015;19:1788–92.
    1. Mohamed S, Shaaban A. The effect of dexmedetomidineon the incidence of postoperative cognitive dysfunction in elderly patients after prolonged abdominal surgery. Am J Transl Res 2017;9:5040–7.
    1. Bilotta F, Qeva E, Matot I. Anesthesia and cognitive disorders: a systematic review of the clinical evidence. Expert Rev Neurother 2016;16:1311–20.
    1. Brioni JD, Varughese S, Ahmed R, et al. A clinical review of inhalation anesthesia with sevoflurane: from early research to emerging topics. J Anesth 2017;31:764–78.
    1. Müller A, Lachmann G, Wolf A, et al. Peri- and postoperative cognitive and consecutive functional problems of elderly patients. Curr Opin Crit Care 2016;22:406–11.
    1. Cheon SY, Kim JM, Kam EH, et al. Cell-penetrating interactomic inhibition of nuclear factor-kappa B in a mouse model of postoperative cognitive dysfunction. Sci Rep 2017;7:13482.
    1. Ma G, Chen C, Jiang H, et al. Ribonuclease attenuates hepatic ischemia reperfusion induced cognitive impairment through the inhibition of inflammatory cytokines in aged mice. Biomed Pharmacother 2017;90:62–8.
    1. Qian XL, Zhang W, Liu MZ, et al. Dexmedetomidine improves early postoperative cognitive dysfunction in aged mice. Eur J Pharmacol 2015;746:206–12.
    1. Zhu YJ, Peng K, Meng XW, et al. Attenuation of neuroinflammation by dexmedetomidine is associated with activation of a cholinergic anti-inflammatory pathway in a rat tibial fracture model. Brain Res 2016;1644:1–8.
    1. Su ZY, Ye Q, Liu XB, et al. Dexmedetomidine mitigates isoflurane-induced neurodegeneration in fetal rats during the second trimester of pregnancy. Neural Regen Res 2017;12:1329–37.
    1. Martin-Flores M, Sakai DM, Honkavaara J, et al. Hemodynamic effects of low-dose atipamezole in isoflurane-anesthetized cats receiving an infusion of dexmedetomidine. J Feline Med Surg 2017;1098612X17722265.
    1. Han XR, Wen X, Wang YJ, et al. MicroRNA-140-5p elevates cerebral protection of dexmedetomidine against hypoxic-ischaemic brain damage via the Wnt/β-catenin signalling pathway. J Cell Mol Med 2018;22:3167–82.
    1. Zhou C, Zhu Y, Liu Z, et al. Effect of dexmedetomidine on postoperative cognitive dysfunction in elderly patients after general anaesthesia: a meta-analysis. J Int Med Res 2016;44:1182–90.
    1. Pasin L, Landoni G, Nardelli P, et al. Dexmedetomidine reduces the risk of delirium, agitation and confusion in critically Ill patients: a meta-analysis of randomized controlled trials. J Cardiothorac Vasc Anesth 2014;28:1459–66.

Source: PubMed

3
Subskrybuj