Dexmedetomidine for Postoperative Cognitive Dysfunction

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Sunnybrook Health Sciences Centre

Disqualifiers: Pregnancy, Major cognitive dysfunction, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether the drug Dexmedetomidine (also known as Precedex) can prevent memory and thinking problems after heart surgery. These issues, known as postoperative cognitive dysfunction (POCD), can persist for weeks or months and impact daily life. The study includes two groups: one receiving standard sedation and the other receiving Dexmedetomidine. It seeks participants aged 60 and over who are scheduled for specific heart surgeries, such as valve replacement or bypass, and will initially recover in a specialized heart care unit. As a Phase 4 trial, this research aims to understand how the already FDA-approved and effective treatment benefits more patients.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. Please consult with the trial coordinators for more details.

What is the safety track record for Dexmedetomidine?

Research shows that dexmedetomidine (DEX) is generally safe for people. In past studies, DEX helped protect brain function after surgery. For instance, it reduced memory and thinking problems, known as postoperative cognitive dysfunction (POCD), in older adults.

The FDA has already approved DEX for other uses, indicating that its safety is well understood. However, like any medication, it can have side effects. Some studies mention that it might affect blood pressure and heart rate. Despite this, most patients have tolerated it well.

In summary, while there are some risks, research suggests that dexmedetomidine is generally safe, especially when healthcare professionals monitor its use. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Unlike the standard sedation protocols commonly used for postoperative cognitive dysfunction, dexmedetomidine offers a unique approach by acting on alpha-2 adrenergic receptors. This mechanism not only helps in sedation but also has the potential to reduce the risk of cognitive impairment after surgery, a significant concern with other sedatives like benzodiazepines and propofol. Researchers are excited about dexmedetomidine because it provides sedation while preserving cognitive function, offering a promising alternative that may enhance recovery and overall patient outcomes.

What evidence suggests that Dexmedetomidine might be an effective treatment for postoperative cognitive dysfunction?

Research shows that dexmedetomidine (DEX) can help reduce problems with thinking and memory after surgery, known as postoperative cognitive dysfunction (POCD). In this trial, participants in the Dexmedetomidine Hydrochloride Group will receive DEX. Studies have found that it significantly lowers the chance of experiencing these cognitive issues, with a risk ratio of 0.47, indicating a reduced likelihood of such problems after surgery. Other research indicates that DEX improves brain function and helps manage thinking and memory better after various surgeries. These findings suggest that DEX could be a promising option for preventing long-term POCD, especially after heart surgery. ^{1 2 3 6 7}

Who Is on the Research Team?

Stephen Choi, MD,MSc,FRCPC

Principal Investigator

Sunnybrook Health Sciences Centre

Sinziana Avramescu, MD,PhD,FRCPC

Principal Investigator

Sunnybrook Health Sciences Centre

Are You a Good Fit for This Trial?

This trial is for individuals aged 60 or older who are scheduled for open heart surgery (CABG or valve replacement) and will recover in the CVICU. They must not have severe pre-existing cognitive issues, a history of certain heart conditions, liver cirrhosis, very slow heartbeat, advanced kidney disease, or be unable to attend follow-up assessments.

Inclusion Criteria

I am scheduled for heart surgery that requires opening my chest, with recovery in the CVICU.

I am 60 years old or older.

Exclusion Criteria

I do not have allergies or conditions that prevent me from taking dexmedetomidine.

I can attend all required study visits and complete tests.

Lack of patient consent

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive dexmedetomidine or standard sedation protocols immediately post-surgery, with dexmedetomidine administered for up to 24 hours

1 day

In-hospital stay

In-hospital Monitoring

Participants are monitored for delirium, hemodynamic stability, and other complications from post-operative day 0 to 10

10 days

Daily assessments

Follow-up

Participants are monitored for POCD, depression, and mild cognitive impairment at 3, 6, and 12 months post-surgery

12 months

Assessments at 3, 6, and 12 months

What Are the Treatments Tested in This Trial?

Interventions

• Dexmedetomidine

Trial Overview The study is testing whether Dexmedetomidine (DEX), given during cardiac surgery, can prevent long-term memory and thinking problems that sometimes occur after such operations. The goal is to see if DEX improves recovery and reduces hospital stays and healthcare costs.

How Is the Trial Designed?

Group I: Standard of Care Group Active Control 1 Intervention

Standard sedation protocols will be followed at the discretion of the attending physician.

Group II: Dexmedetomidine Hydrochloride Group Active Control 1 Intervention

Patients will receive a loading dose of 1 μg/kg dexmedetomidine prior to transfer to CVICU over 20 min immediately postoperative, followed by continuous infusion of 0.1- 1.0 μg/kg/h for up to 24 hours or until patient is ready for discharge from CVICU (whichever is earlier).

Dexmedetomidine is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Precedex for:

• Sedation in intensive care settings
• Procedural sedation

Approved in United States as Precedex for:

• Sedation in intensive care settings
• Procedural sedation

Approved in Canada as Precedex for:

• Sedation in intensive care settings
• Procedural sedation

Approved in Japan as Precedex for:

• Sedation in intensive care settings
• Procedural sedation

Who Is Running the Clinical Trial?

Sunnybrook Health Sciences Centre

Lead Sponsor

Trials

693

Recruited

1,569,000+

Published Research Related to This Trial

In a study of 30 patients with liver dysfunction undergoing percutaneous arterial chemoembolization for hepatocellular carcinoma, dexmedetomidine sedation was successfully used in all cases, demonstrating its feasibility for this procedure.

The sedation was generally safe, with only minor adverse events reported in 3 patients, and no serious complications requiring treatment, indicating that dexmedetomidine can be a reliable option for sedation in patients with liver issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Feasibility and Safety of Dexmedetomidine Sedation in Transarterial Embolization for Hepatocellular Carcinoma with Hepatitis C-Related Cirrhosis]. Komemushi, A., Suzuki, S., Sano, A., et al.[2015]

A meta-analysis of 14 randomized controlled trials involving 1626 elderly adults showed that dexmedetomidine significantly reduces the incidence of postoperative cognitive dysfunction (POCD), with a risk ratio of 0.47, indicating nearly a 53% reduction in risk.

The most robust evidence for dexmedetomidine's effectiveness in preventing POCD came from studies using the Mini-Mental State Examination (MMSE) for diagnosis, suggesting it may be a valuable preventative treatment for cognitive issues after surgery in older patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influence of dexmedetomidine on postoperative cognitive dysfunction in the elderly: A meta-analysis of randomized controlled trials. Yu, H., Kang, H., Fan, J., et al.[2022]

Dexmedetomidine (DEX) is an effective sedative with neuroprotective properties, showing improved outcomes in ICU patients and potential as a non-opioid analgesic, which is important for reducing opioid-related side effects.

While DEX has significant benefits for the nervous system, clinicians must be aware of potential adverse effects like hypotension and bradycardia, which can be managed with medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dexmedetomidine as an Analgesic Agent with Neuroprotective Properties: Experimental and Clinical Aspects. Bozorgi, H., Zamani, M., Motaghi, E., et al.[2021]

Dexmedetomidine is commonly used as a safe sedative during surgeries, but there are rare cases where it can lead to serious complications, such as cardiac arrest.

In this report, a 76-year-old woman experienced cardiac arrest during a pacemaker lead extraction procedure while being treated with dexmedetomidine, highlighting the need for careful monitoring in older patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dexmedetomidine related cardiac arrest in a patient with permanent pacemaker; a cautionary tale. Shah, AN., Koneru, J., Nicoara, A., et al.[2013]

Dexmedetomidine significantly reduces the incidence of postoperative cognitive dysfunction (POCD) in elderly adults after general anesthesia, with a relative risk of 0.59 based on 13 randomized controlled trials.

The use of dexmedetomidine also improves cognitive function as measured by the Mini-Mental State Examination (MMSE) score on the first postoperative day, indicating its potential benefits in enhancing recovery after surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of dexmedetomidine on postoperative cognitive dysfunction in elderly patients after general anaesthesia: A meta-analysis. Zhou, C., Zhu, Y., Liu, Z., et al.[2022]

In elderly patients undergoing major surgery, continuous infusion of dexmedetomidine (DEX) at doses of 200 μg or 400 μg significantly reduced the incidence of postoperative delirium (POD) and early postoperative cognitive dysfunction (POCD) compared to lower doses.

DEX 400 μg was particularly effective in reducing early POCD in patients who had open surgery, and this treatment did not lead to increased sedation, pain intensity, or side effects, indicating its safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effect and Optimal Dosage of Dexmedetomidine Plus Sufentanil for Postoperative Analgesia in Elderly Patients With Postoperative Delirium and Early Postoperative Cognitive Dysfunction: A Single-Center, Prospective, Randomized, Double-Blind, Controlled Trial. Zhao, W., Hu, Y., Chen, H., et al.[2022]

In a study of 24 pediatric patients undergoing airway reconstruction, dexmedetomidine was found to be well tolerated and safe, particularly for short-term intubation, with no significant adverse effects reported.

Dexmedetomidine may serve as a beneficial alternative to propofol for sedation during the periextubation period, allowing for easily reversible sedation, although further research is needed to explore its long-term safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dexmedetomidine use in pediatric airway reconstruction. Silver, AL., Yager, P., Purohit, P., et al.[2022]

In a study involving 91 pediatric patients, dexmedetomidine was found to be a well-tolerated alternative sedative for non-intubated moderate or deep sedation, with a low incidence of serious adverse events.

While respiratory depression and hypotension were the most common treatment-emergent adverse events, they were manageable and consistent with dexmedetomidine's known safety profile, indicating its potential for safe use in children during elective procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase IV, Open-Label, Safety Study Evaluating the Use of Dexmedetomidine in Pediatric Patients Undergoing Procedure-Type Sedation. Jooste, EH., Hammer, GB., Reyes, CR., et al.[2020]

In a study of 83 pediatric patients undergoing inguinal hernia repair, intranasal administration of dexmedetomidine resulted in lower rates of emergence agitation (4.76%) compared to intravenous administration (21.95%), indicating a more favorable awakening experience.

Patients receiving intranasal dexmedetomidine also showed better cognitive, language, and motor scores three days post-surgery, with a significantly lower incidence of cognitive dysfunction (4.76% vs. 21.95% for IV), suggesting that this route of administration may enhance early cognitive recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of different routes of administration on early cognitive function following inguinal hernia repair. Huang, J., Deng, B., Shuai, J., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10019181/

Effectiveness of dexmedetomidine on postoperative ... The results of this study showed that dexmedetomidine could effectively manage POCD in elderly patients with fracture.

2. frontiersin.org frontiersin.org/journals/neurology/articles/10.3389/fneur.2024.1422049/full

Effects of dexmedetomidine on early postoperative ... Our meta-analysis showed that DEX improves neurological outcomes in different surgical and anesthesia approaches, consistent with previous ...

3. cardiothoracicsurgery.biomedcentral.com cardiothoracicsurgery.biomedcentral.com/articles/10.1186/s13019-021-01736-z

The effect of intraoperative dexmedetomidine on cognitive ... At the present study, our meta-analysis clearly showed that the intraoperative use of DEX could obviously alleviate cognitive dysfunction, lower ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9392542/

Influence of dexmedetomidine on postoperative cognitive ... Pooled results of RCTs with MMSE showed that Dex significantly reduced the incidence of POCD (risk ratio: 0.47, 95% confidence interval: 0.37–0.60, p < 0.001) ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT03480061

Dexmedetomidine to Reduce the Incidence of POCD After ... The investigators propose to investigate the role of Dexmedetomidine (DEX) in preventing long-term POCD after cardiac surgery and enhancing early postoperative ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12408329/

Effect of dexmedetomidine on postoperative cognitive ... In conclusion, this meta-analysis suggests that DEX has a protective effect on the cognitive function of patients with GICs undergoing RS.

7. trialsjournal.biomedcentral.com trialsjournal.biomedcentral.com/articles/10.1186/s13063-023-07110-9

Effect of dexmedetomidine on postoperative cognitive ... This trial aims to assess whether dexmedetomidine can reduce the incidence of postoperative cognitive dysfunction in elderly orthopaedic patients.