Clinical trial NCT03480061: Dexmedetomidine to Reduce the Incidence of POCD After Open Cardiac Surgery
Official title: Dexmedetomidine to Reduce the Incidence of Persistent Cognitive Dysfunction After Open Cardiac Surgery: A Pilot Randomized Trial
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE4
Conditions: Delirium
Postoperative Cognitive Dysfunction
Dexmedetomidine
Cognitive Impairment
Depression
Lead sponsor: Sunnybrook Health Sciences Centre
Sponsor class: OTHER
First posted: 2018-03-27
Enrollment: 90
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

Detailed description: 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.

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 (for full multicentre trial).

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 4), 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).

Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

* Lack of patient consent
* Pregnant or nursing females
* Pre-operative major cognitive dysfunction (CogState Brief Battery score \< 80)
* Aortic arch replacement/re-implantation (Bentalls)
* 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 timepoints)

Primary outcomes:
measure: Rate of recruitment
timeFrame: 12 Months
Secondary outcomes:
measure: Completion of follow-up assessments
timeFrame: 3 months
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
Study officials:
affiliation: Sunnybrook Health Sciences Centre
name: Stephen Choi, MD,MSc,FRCPC
role: PRINCIPAL_INVESTIGATOR
affiliation: Sunnybrook Health Sciences Centre
name: Sinziana Avramescu, MD,PhD,FRCPC
role: PRINCIPAL_INVESTIGATOR
References: