Intraoperative Infusion of Methylene Blue for Prevention of Postoperative Delirium and Cognitive Dysfunction in Elderly Patients Undergoing Major Elective Noncardiac Surgery

October 26, 2020 updated by: Jun Zhang, Fudan University

Intraoperative Infusion of Methylene Blue for Prevention of Postoperative Delirium and Cognitive Dysfunction in Elderly Patients Undergoing Major Elective Noncardiac and Nonneurosurgical Surgery

Postoperative neurocognitive impairments often occur in elderly patients undergoing anesthesia and non-cardiac surgery, including postoperative delirium (POD) and postoperative cognitive dysfunction (POCD). These disorders are often associated with increased mortality and morbidity, prolonged length of hospital stay, functional and cognitive decline with nursing home or long-term care facility placement. Until now highly effective intervention has not been established yet. As a mitochondrial protective agent, the role of methylene blue(MB) in preventing elderly patients from POD/POCD is unknown.Therefore, investigators design this study to validate its prevention against POD/POCD and the aim of this study is to evaluate the efficacy and safety of perioperative administration of MB for POD/POCD prevention.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Postoperative neurocognitive impairments often occur in elderly patients undergoing major surgery, including postoperative delirium(POD) characterized by an acute change in cognition with altered consciousness and impaired attention, and postoperative cognitive dysfunction(POCD) mainly manifested as reduced ability of learning and memory. POD and POCD are major complications that cause disability and distress for millions of patients annually.In 2004, there was an estimated 5-40% incidence in 7.9 million patients over 65 years who had a surgical procedure subsequently experiencing either POD or POCD.The underlying pathophysiology of Postoperative neurocognitive impairments is increasingly understood, implicating a prominent role of neuroinflammation, oxidative stress and mitochondrial dysfunction.Recent experimental evidences reveal that mitochondrial dysfunction is increasingly considered a significant contributor to the development of POD and POCD.

Methylene blue(MB) is a diaminophenothiazine with a long history of clinical use due to its minimal side effect profiles. MB currently is used for treatment of methemoglobinemia, carbon monoxide poisoning, and vasoplegic syndrome as well as for surgical staining. MB could diffuse rapidly into brain and accumulate in the cytoplasm and mitochondria of neurons. In recent years its role as a mitochondrial protective agent has elicited much of its renewed interest, especially, studies have shown that MB has established its neuroprotective effects against ischemic stroke, post-chemotherapy-induced Encephalopathy and neurodegenerative diseases caused by Alzheimer's disease(AD) and psychoses.To date, there is no trials have examined the role of intraoperative MB administration in prevention of POD and POCD in elderly patients undergoing non-cardiac surgery, who have preoperative normal neurocognitive function. Therefore, investigators design this study to evaluate the efficacy and safety of perioperative administration of MB for POD/POCD prevention. It's an entirely novel therapy for postoperative neurocognitive disorders and will have high clinical translatable value if this intervention is found to be beneficial.

Study Type

Interventional

Enrollment (Actual)

248

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Shanghai
      • Shanghai, Shanghai, China, 200040
        • Huashan Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

58 years to 78 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • aged 60-80 years old
  • planning to undergo non-cardiac and non-neurosurgical surgery (e.g..thoracic, orthopaedic, urologic and major abdominal surgeries) under general anesthesia
  • MMSE>20
  • Liver and kidney function are normal
  • Patients have the ability to act in full spirit, understand and sign the informed consent, and are willing to complete the whole research process.

Exclusion Criteria:

  • Patients with personal history of allergy to methylene blue
  • Emergency Surgery
  • Patients have 6-phospho-glucose dehydrogenase deficiency (vicia faba disease)
  • Patients have recent drug administration that may lead to drug interactions(e.g..SSRIs, SNRIs)
  • Patient with a history of major head trauma
  • Patients with a history of drug or alcohol abuse
  • Patient has serious mental or neurological disorders
  • Patients with severe language, hearing and visual impairment
  • Patients have serious medical diseases(e.g..heart failure, acute stage of myocardial infarction or respiratory failure)
  • Illiteracy
  • Patients have participated in other clinical trials in the last 3 months.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Methylene Blue
2mg/kg MB diluted with normal saline into total 50 ml volume intravenous administration after induction of anesthesia within one hour.
Drug: Methylene Blue
2mg/kg MB diluted with normal saline into total 50 ml volume intravenous administration after induction of anesthesia within one hour.
Placebo Comparator: Control
normal saline in total 50 ml volume intravenous administration after induction of anesthesia within one hour.
Drug: Placebo
normal saline in total 50 ml volume intravenous administration after induction of anesthesia within one hour.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of postoperative delirium(POD)
Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 5 days.
the effectiveness of MB in reducing the incidence of POD compared with placebo in elderly patients undergoing major elective non-cardiac surgery.
Participants will be followed for the duration of hospital stay, an expected average of 5 days.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of postoperative cognitive dysfunction (POCD)
Time Frame: Up to 3 month after surgery
the effectiveness of MB in reducing the incidence of POCD compared with placebo in elderly patients undergoing major elective non-cardiac surgery.
Up to 3 month after surgery
Safety Assessments: incidence of perioperative adverse events
Time Frame: the whole perioperative period
the incidence of perioperative adverse events to reflect safety of intraoperative intravenous 2mg/kg MB administration
the whole perioperative period
Oxidative Stress Biomarkers
Time Frame: the day before surgery and postoperative one day
the Changes in levels of oxidative stress biomarkers( superoxide dismutase(SOD) and homocysteine(HCY) )
the day before surgery and postoperative one day

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fudan University

Investigators

  • Principal Investigator: Jun Zhang, PhD, Huashan Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 14, 2019

Primary Completion (Actual)

April 30, 2020

Study Completion (Actual)

July 30, 2020

Study Registration Dates

First Submitted

March 31, 2020

First Submitted That Met QC Criteria

April 8, 2020

First Posted (Actual)

April 10, 2020

Study Record Updates

Last Update Posted (Actual)

October 27, 2020

Last Update Submitted That Met QC Criteria

October 26, 2020

Last Verified

October 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • KY2019-274

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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