Cognitive Outcomes After Dexmedetomidine Sedation in Cardiac Surgery Patients

Официальное название

Cognitive Outcomes After Dexmedetomidine Sedation in Cardiac Surgery Patients: CODEX Trial

Обзор

Anesthesia is a drug induced, reversible, comatose state that facilitates surgery and it is widely assumed that cognition returns to baseline after anesthetics have been eliminated. However, many patients have persistent memory impairment for weeks to months after surgery. Cardiac surgery appears to carry the highest risk of postoperative cognitive dysfunction (POCD). These cognitive deficits are associated with increased mortality, prolonged hospital stay and loss of independence. The investigators propose to investigate the role of Dexmedetomidine (DEX) in preventing long-term POCD after cardiac surgery and enhancing early postoperative recovery. It is anticipated that DEX will be the first effective preventative therapy for POCD, improve patient outcomes, and reduce length of stay and healthcare costs.

Подробное описание

Dexmedetomidine (DEX), a highly potent and selective α2-adrenoceptors (α2R) agonist used in clinical practice for sedation, analgesia, and anxiolysis, was recently shown to have beneficial effects on early cognitive changes by reducing delirium in humans. It also reduced memory impairment after surgery and isoflurane anesthesia, both in elderly mice (20-22 months) and in pups exposed to anesthesia in the early postnatal period. Importantly, co-treatment with DEX has been shown to restore learning and memory function in rats exposed to propofol in utero. Therefore, the investigators set out to investigate whether DEX has an effect on cognitive dysfunction months after surgery and whether it accelerates cognitive recovery from anesthesia and surgery.

This is a double blinded, multi-site trial facilitated by Clinical Trials Ontario (CTO). Participants will be randomized 1:1 in permuted blocks of 4 to 8. The randomization sequence will be computer generated and stratified by 2 factors, planned procedure (CABG/CABG + valve or valve only procedure) and study site.

In hospital outcomes include delirium (assessed twice daily post-operative day (POD) 0-10, death, hemodynamic instability requiring vasopressors, time to extubation, re-intubation (and reason), length of stay (in Cardiovascular Intensive Care Unit and total hospital), POCD, depressive symptoms between POD 4-10, post-operative complications (infection \[surgical site, sepsis, pneumonia\], myocardial infarction, renal replacement therapy, re-operation, cumulative opioid consumption (to POD 5), in-hospital mortality.

Post-operative outcomes include POCD (3/6/12 months), depression (3/6/12 months), mild cognitive impairment (MCI) at 3/6/12 months (defined as 1-2 standard deviations below age matched controls), persistent surgical site pain at sternotomy/thoracotomy/graft harvest site (Brief Pain Inventory, 3/6/12 months), recovery (3,6, 12 months).

Вмешательства

• Препарат Dexmedetomidine Hydrochloride Group
  Dexmedetomidine will be initiated prior to transfer to the CVICU with loading dose of 1.2 ug/kg over approximately 20-60 minutes. This will be followed by an infusion at 0.3 ug/kg/h in CVICU for up to 12 hours from the time DEX infusion started or until the patient is ready for discharge from the CVICU (whichever is earlier). Any additional sedatives necessary at the discretion of ICU.

Первичные конечные точки

• Post-operative cognitive dysfunction [Срок оценки: 3 months]

Вторичные конечные точки (10)

• Post-operative cognitive dysfunction (POCD) at 1 week, 6 months, 12 months after surgery [Срок оценки: 1 week, 6 and 12 months]
• Delirium [Срок оценки: Anytime up to post-operative day 10]
• Length of stay [Срок оценки: An average of 5 -14 days]
• Depressive symptoms [Срок оценки: 3, 6, and 12 months]
• Persistent Surgical Site Pain [Срок оценки: 3, 6, and 12 months]
• Quality of Surgical Recovery [Срок оценки: 3, 6, 12 months]
• Mild Cognitive Impairment [Срок оценки: 3, 6, and 12 months]
• In-hospital mortality for index surgery [Срок оценки: through initial inpatient admission, average of 1 week]
• Opioid consumption to POD 4 [Срок оценки: 4 days]
• Time to extubation [Срок оценки: through ICU stay, average of 12 hours]

Критерии участия

Критерии включения

• Planned CABG (+/- valve, including off-pump) or valve replacement via sternotomy/thoracotomy, with initial recovery in the Cardiovascular Intensive Care Unit (CVICU)
• Age ≥60

Критерии исключения

• Lack of patient consent
• Pre-operative major cognitive dysfunction (CogState Brief Battery score < 80) at screening
• Aortic arch replacement/re-implantation (surgery requiring hypothermic circulatory arrest, e.g. Bentall procedure)
• Allergy/contraindication to dexmedetomidine (untreated 2nd degree type 2 or 3rd degree heart block (pacemaker), cirrhosis, HR < 50 , grade 4 LV, renal failure or on renal replacement therapy)
• Unlikely to comply with study assessments (e.g. no fixed address, cannot complete cognitive tests at the 3, 6, and 12 month time points)

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Профилактика

Центры проведения

Канада · 8 центров

• Royal Columbian Hospital — Vancouver
• St. Paul's Hospital — Vancouver
• London Health Sciences — London
• Sunnybrook Health Sciences Centre — Toronto
• St. Michael's Hospital — Toronto
• Toronto General Hospital — Toronto
• Laval University — Québec
• University of Saskatchewan — Saskatoon

Публикации

• Choi S, Jerath A, Jones P, Avramescu S, Djaiani G, Syed S, Saha T, Kaustov L, Kiss A, D'Aragon F, Hedlin P, Rajamohan R, Couture EJ, Singh A, Mapplebeck JC, Wong S, Orser BA. Cognitive Outcomes after DEXmedetomidine sedation in cardiac surgery: CODEX randomised controlled trial protocol. BMJ Open. 2021 Apr 13;11(4):e046851. doi: 10.1136/bmjopen-2020-046851. PMID 33849856

Идентификаторы

NCT: NCT04289142 · 1743

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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