The Effects of Dexmedetomidine on Perioperative Neurocognitive Outcomes After Cardiac Surgery: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

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 = 0.27) or incidence of hemodynamic instability (OR 1.14, 95% CI 0.59-2.18, P = 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.

The Effects of Dexmedetomidine on Perioperative Neurocognitive Outcomes After Noncardiac Surgery: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Objective: The 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. Background: Dexmedetomidine (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. Methods: Prospective 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. Results: Among 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). Conclusions: Dexmedetomidine 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.

Cognitive Outcomes after DEXmedetomidine sedation in cardiac surgery: CODEX randomised controlled trial protocol.

INTRODUCTION: Older 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 ANALYSIS: CODEX 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 DISSEMINATION: CODEX 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 NUMBER: NCT04289142.