Data_Sheet_1_Is Perioperative Dexmedetomidine Associated With a Reduced Risk of Perioperative Neurocognitive Disorders Following Cardiac Surgery? A Systematic Review and Meta-Analysis With Trial Sequential Analysis of Randomized Controlled Trials.docx

Background: To assess the effect of dexmedetomidine on the reducing risk of perioperative neurocognitive disorders (PNDs) following cardiac surgery.
Methods: A systematic review and meta-analysis with trial sequential analysis (TSA) of randomized controlled trials were performed. PubMed, Embase, Cochrane Library, and CNKI databases (to August 16, 2020) were searched for relevant articles to analyze the incidence of PND for intraoperative or postoperative dexmedetomidine administration after cardiac surgery. PND included postoperative cognitive dysfunction (POCD) and postoperative delirium (POD).
Results: A total of 24 studies with 3,610 patients were included. Compared with the control group, the incidence of POD in the dexmedetomidine group was significantly lower (odds ratio [OR]: 0.59, 95% CI: 0.43–0.82, P = 0.001), with firm evidence from TSA. Subgroup analyses confirmed that dexmedetomidine reduced the incidence of POD with firm evidence following coronary artery bypass grafting surgery (OR: 0.45, 95% CI: 0.26–0.79, P = 0.005), and intervention during the postoperative period (OR: 0.48, 95% CI: 0.34–0.67, P < 0.001). Furthermore, the incidence of POD in the dexmedetomidine group was also decreased in mixed cardiac surgery (OR: 0.68, 95% CI: 0.47–0.98, P = 0.039). Irrespective of whether “Confusion Assessment Method/Confusion Assessment Method for intensive care unit” or “other tools” were used as diagnostic tools, the results showed a decreased risk of POD in the dexmedetomidine group. There was no significant difference in the incidence of POCD (OR: 0.47, 95% CI: 0.22–1.03, P = 0.060) between the two groups, but this result lacked firm evidence from TSA.
Conclusion: The administration of dexmedetomidine during the perioperative period reduced the incidence of POD in patients after cardiac surgery, but there was no significant benefit in the incidence of POCD. The effect of dexmedetomidine on the incidence of POD or POCD following different types of surgery and the optimal dose and timing of dexmedetomidine warrant further investigation.
Trial registration: PROSPERO registration number: CRD42020203980. Registered on September 13, 2020.

背景：旨在评估右美托咪定（dexmedetomidine）对降低心脏手术后围手术期神经认知障碍（perioperative neurocognitive disorders, PNDs）发生风险的作用。
方法：本研究针对随机对照试验开展系统评价与meta分析，并辅以试验序贯分析（trial sequential analysis, TSA）。检索PubMed、Embase、Cochrane图书馆及中国知网（CNKI）数据库截至2020年8月16日的相关文献，分析心脏手术患者术中或术后使用右美托咪定后PNDs的发生情况。PNDs涵盖术后认知功能障碍（postoperative cognitive dysfunction, POCD）与术后谵妄（postoperative delirium, POD）。
结果：最终纳入24项研究，共3610例患者。与对照组相比，右美托咪定组患者的POD发生率显著降低（比值比（odds ratio, OR）：0.59，95%置信区间（95% CI）：0.43–0.82，P = 0.001），试验序贯分析证实了该结果的可靠性。亚组分析显示，在冠状动脉旁路移植术患者中，右美托咪定可显著降低POD发生率（OR：0.45，95%CI：0.26–0.79，P = 0.005）；在术后干预亚组中，同样得到了可靠的阳性结果（OR：0.48，95%CI：0.34–0.67，P < 0.001）。此外，混合心脏手术患者的POD发生率也有所降低（OR：0.68，95%CI：0.47–0.98，P = 0.039）。无论采用意识模糊评估法（Confusion Assessment Method, CAM）/重症监护病房意识模糊评估法（Confusion Assessment Method for intensive care unit, CAM-ICU）还是其他工具作为诊断工具，右美托咪定组的POD发生风险均显著降低。两组患者的POCD发生率无显著差异（OR：0.47，95%CI：0.22–1.03，P = 0.060），但该结果未得到试验序贯分析的证实。
结论：围手术期使用右美托咪定可降低心脏手术后患者的POD发生率，但未显著改善POCD的发生风险。不同手术类型下右美托咪定对POD或POCD发生率的影响，以及右美托咪定的最佳给药剂量与时机，仍需进一步研究探索。
试验注册：PROSPERO注册号：CRD42020203980。2020年9月13日完成注册。