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

Fudan University

Status

Completed

Conditions

Postoperative Delirium

Postoperative Cognitive Dysfunction

Treatments

Drug: Methylene Blue

Drug: Placebo

Study type

Interventional

Funder types

Other

Identifiers

NCT04341844

KY2019-274

Details and patient eligibility

About

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.

Full 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.

Enrollment

248 patients

Sex

All

Ages

60 to 80 years old

Volunteers

No Healthy Volunteers

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.