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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

ABSTRACT: 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.

SUBMITTER: Xiong X

PROVIDER: S-EPMC8511308 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ObjectiveThe purpose of this review is to examine the effect of dexmedetomidine on delayed neurocognitive recovery (dNCR; cognitive dysfunction ≥1 week postoperative) after major noncardiac surgery.BackgroundDexmedetomidine (DEX) effectively reduces delirium in the intensive care unit and reportedly attenuates cognitive decline following major noncardiac surgery. Ascertaining the true effect on postoperative cognition is difficult because studies are limited by suboptimal selection of cognitive assessment tools, timing of testing, and criteria for defining significant cognitive decline.MethodsProspective randomized trials comparing perioperative DEX to placebo for major noncardiac surgery assessing cognitive function ≥1 week postoperative were included. Pediatric, nonhuman, and non-English trials, and those where executive function was not assessed were excluded. Data were abstracted by 3 reviewers independently and in parallel according to PRISMA guidelines. The a priori binary primary outcome is dNCR defined as cognitive function declining by the minimal clinically important difference or accepted alternate measure (eg, Reliable Change Index ≥1.96). Bias was assessed with the Cochrane Collaboration tool. Data were pooled using a random effects model.ResultsAmong 287 citations identified, 26 (9%) met criteria for full-text retrieval. Eleven randomized trials (1233 participants) were included for qualitative analysis, and 7 trials (616 participants) were included for meta-analysis of dNCR. Dexmedetomidine did not reduce the incidence of dNCR significantly (OR 0.57, 95% CI 0.30-1.10, P = 0.09) compared with placebo. There was no difference in the incidence of delirium (OR 0.94, 95% CI 0.55-1.63, P = 0.83) and a higher incidence of hemodynamic instability (OR 2.11, 95% CI 1.22-3.65, P = 0.008).ConclusionsDexmedetomidine does not reduce dNCR 1 week after major noncardiac surgery. This meta-analysis does not yet support the use of perioperative DEX to improve short term cognitive outcomes at this time; trials underway may yet change this conclusion while larger trials are needed to refine the point estimate of effect and examine long-term cognitive outcomes.

Project description:William Morton introduced the world to ether anesthesia for use during surgery in the Bullfinch Building of the Massachusetts General Hospital on October 16, 1846. For nearly two centuries, the prevailing wisdom had been that the effects of general anesthetics were rapidly and fully reversible, with no apparent long-term adverse sequelae. Despite occasional concerns of a possible association between surgery and anesthesia with dementia since 1887 (Savage, 1887), our initial belief was robustly punctured following the publication in 1998 of the International Study of Post-Operative Cognitive Dysfunction [ISPOCD 1] study by Moller et al. (1998) in The Lancet, in which they demonstrated in a prospective fashion that there were in fact persistent adverse effects on neurocognitive function up to 3 months following surgery and that these effects were common. Since the publication of that landmark study, significant strides have been made in redefining the terminology describing cognitive dysfunction, identifying those patients most at risk, and establishing the underlying etiology of the condition, particularly with respect to the relative contributions of anesthesia and surgery. In 2018, the International Nomenclature Consensus Working Group proposed new nomenclature to standardize identification of and classify perioperative cognitive changes under the umbrella of perioperative neurocognitive disorders (PND) (Evered et al., 2018a). Since then, the new nomenclature has tried to describe post-surgical cognitive derangements within a unifying framework and has brought to light the need to standardize methodology in clinical studies and motivate such studies with hypotheses of PND pathogenesis. In this narrative review, we highlight the relevant literature regarding recent key developments in PND identification and management throughout the perioperative period. We provide an overview of the new nomenclature and its implications for interpreting risk factors identified by clinical association studies. We then describe current hypotheses for PND development, using data from clinical association studies and neurophysiologic data where appropriate. Finally, we offer broad clinical guidelines for mitigating PND in the perioperative period, highlighting the role of Brain Enhanced Recovery After Surgery (Brain-ERAS) protocols.

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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

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