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IntroductionOlder patients undergoing cardiac surgery carry the highest risk for developing major postoperative neurocognitive disorder (postoperative NCD or P-NCD) with up to 25% incidence 3 months after surgery. P-NCD is associated with significant morbidity, mortality, loss of independence, premature retirement and increased healthcare costs. This multicentre randomised trial is investigating the efficacy of postoperative dexmedetomidine sedation in reducing the incidence of major P-NCD after cardiac surgery compared with standard protocols. CODEX will be the largest interventional trial with major P-NCD as the primary outcome.Methods and analysisCODEX is recruiting patients ≥60 years old, undergoing elective cardiac surgery and without pre-existing major cognitive dysfunction or dementia. Eligible participants are randomised to receive postoperative dexmedetomidine or standard institutional sedation protocols in the intensive care unit. Baseline preoperative cognitive function is assessed with the computer-based Cogstate Brief Battery. The primary outcome, major P-NCD, 3 months after surgery is defined as a decrease in cognitive function ≥1.96 SD below age-matched, non-operative controls. Secondary outcomes include delirium, major P-NCD at 6/12 months, depressive symptoms, mild P-NCD and quality of surgical recovery at 3/6/12 months. The specific diagnostic criteria used in this protocol are consistent with the recommendations for clinical assessment and management of NCD from the Nomenclature Consensus Working Group on perioperative cognitive changes. Intention-to-treat analysis will compare major P-NCD at 3 months between study groups.Ethics and disseminationCODEX was approved by Sunnybrook Health Sciences Centre Research Ethics Board (REB) (Project ID 1743). This will be the first multicentre, randomised controlled trial to assess the efficacy of a pharmacological intervention to reduce the incidence of major P-NCD after cardiac surgery in patients ≥60 years old. Dissemination of the study results will include briefings of key findings and interpretation, conference presentations and peer-reviewed publications.Trial registration numberNCT04289142.

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Objective: The purpose of this systematic review and meta-analysis is to examine the effect of DEX on delayed dNCR (cognitive dysfunction ! 1 week postoperative) after cardiac surgery. Background: DEX has salutary effects on cognitive outcomes following cardiac surgery, however, studies are limited by inconsistent assessment tools, timing, and definitions of dysfunction. It is imperative to identify accurate point estimates of effect of DEX on clinically relevant changes in cognitive function. Methods: Randomized trials of adults undergoing cardiac surgery comparing perioperative DEX to placebo or alternate sedation and assessing cognitive function !1 week postoperative were included. Data was abstracted by three reviewers independently and in parallel according to PRISMA guidelines. The primary outcome is dNCR. To classify as dNCR, cognitive function must decrease by at least the minimal clinically important difference or accepted alternate measure (eg, Reliable Change Index !1.96). Bias was assessed with the Cochrane Collaboration tool. Data was pooled using a random effects model. Results: Nine trials (942 participants) were included in qualitative analysis, of which seven were included in the meta-analysis of dNCR. DEX reduced the incidence of dNCR (OR 0.39, 95% CI 0.25-0.61, P < 0.0001) compared to placebo/no DEX. There was no difference in the incidence of delirium (OR 0.69, 95% CI 0.35-1.34, P ¼ 0.27) or incidence of hemodynamic instability (OR 1.14, 95% CI 0.59-2.18, P ¼ 0.70) associated with perioperative DEX. Conclusions: DEX reduced the incidence of dNCR 1 week after cardiac surgery. Although this meta-analysis demonstrates short term cognitive outcomes are improved after cardiac surgery with perioperative DEX, future trials examining long term cognitive outcomes, using robust cognitive assessments, and new perioperative neurocognitive disorders nomenclature with objective diagnostic criteria are necessary.