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

NCT04341844 | Completed DMC

• 1 other identifier: KY2019-274
• Study Type: interventional
• Target: 248
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Postoperative Delirium; Postoperative Cognitive Dysfunction

Outcome Measures

Primary Outcomes (1)

• Incidence of postoperative delirium(POD)

  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 Outcomes (3)

• Incidence of postoperative cognitive dysfunction (POCD)

  Up to 3 month after surgery

• Safety Assessments: incidence of perioperative adverse events

  the whole perioperative period

• Oxidative Stress Biomarkers

  the day before surgery and postoperative one day

Study Arms (2)

Methylene Blue

EXPERIMENTAL

2mg/kg MB diluted with normal saline into total 50 ml volume intravenous administration after induction of anesthesia within one hour.

Drug: Methylene Blue

Control

PLACEBO COMPARATOR

normal saline in total 50 ml volume intravenous administration after induction of anesthesia within one hour.

Drug: Placebo

Interventions

Methylene Blue DRUG

2mg/kg MB diluted with normal saline into total 50 ml volume intravenous administration after induction of anesthesia within one hour.

Methylene Blue

Placebo DRUG

normal saline in total 50 ml volume intravenous administration after induction of anesthesia within one hour.

Control

Eligibility Criteria

• Age: 60 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Fudan University: lead

Study Sites (1)

Huashan Hospital

Shanghai, Shanghai Municipality, 200040, China

Location

Related Publications (4)

• Deiner S, Luo X, Lin HM, Sessler DI, Saager L, Sieber FE, Lee HB, Sano M; and the Dexlirium Writing Group; Jankowski C, Bergese SD, Candiotti K, Flaherty JH, Arora H, Shander A, Rock P. Intraoperative Infusion of Dexmedetomidine for Prevention of Postoperative Delirium and Cognitive Dysfunction in Elderly Patients Undergoing Major Elective Noncardiac Surgery: A Randomized Clinical Trial. JAMA Surg. 2017 Aug 16;152(8):e171505. doi: 10.1001/jamasurg.2017.1505. Epub 2017 Aug 16.

  PMID: 28593326 RESULT

• Avidan MS, Maybrier HR, Abdallah AB, Jacobsohn E, Vlisides PE, Pryor KO, Veselis RA, Grocott HP, Emmert DA, Rogers EM, Downey RJ, Yulico H, Noh GJ, Lee YH, Waszynski CM, Arya VK, Pagel PS, Hudetz JA, Muench MR, Fritz BA, Waberski W, Inouye SK, Mashour GA; PODCAST Research Group. Intraoperative ketamine for prevention of postoperative delirium or pain after major surgery in older adults: an international, multicentre, double-blind, randomised clinical trial. Lancet. 2017 Jul 15;390(10091):267-275. doi: 10.1016/S0140-6736(17)31467-8. Epub 2017 May 30.

  PMID: 28576285 RESULT

• Tucker D, Lu Y, Zhang Q. From Mitochondrial Function to Neuroprotection-an Emerging Role for Methylene Blue. Mol Neurobiol. 2018 Jun;55(6):5137-5153. doi: 10.1007/s12035-017-0712-2. Epub 2017 Aug 24.

  PMID: 28840449 RESULT

• Gonzalez-Lima F, Barksdale BR, Rojas JC. Mitochondrial respiration as a target for neuroprotection and cognitive enhancement. Biochem Pharmacol. 2014 Apr 15;88(4):584-93. doi: 10.1016/j.bcp.2013.11.010. Epub 2013 Dec 4.

  PMID: 24316434 RESULT

MeSH Terms

Conditions

Emergence Delirium; Postoperative Cognitive Complications

Interventions

Methylene Blue

Condition Hierarchy (Ancestors)

Delirium; Confusion; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Neurocognitive Disorders; Mental Disorders; Cognitive Dysfunction; Cognition Disorders

Intervention Hierarchy (Ancestors)

Phenothiazines; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Jun Zhang, PhD

  Huashan Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 31, 2020
• First Posted: April 10, 2020
• Study Start: January 14, 2019
• Primary Completion: April 30, 2020
• Study Completion: July 30, 2020
• Last Updated: October 27, 2020

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)