Intraoperative Infusion of Methylene Blue for Prevention of Postoperative Delirium and Cognitive Dysfunction in Elderly Patients Undergoing Major Elective Noncardiac Surgery
Condition: Postoperative Delirium; Postoperative Cognitive Dysfunction
MeSH terms: Delirium; Emergence Delirium; Postoperative Cognitive Complications; Cognitive Dysfunction
Study type: Interventional

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.
    

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.
    

Intervention name(s): Methylene Blue; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): 2mg/kg MB diluted with normal saline into total 50 ml volume intravenous administration after induction of anesthesia within one hour.; normal saline in total 50 ml volume intravenous administration after induction of anesthesia within one hour.
Intervention MeSH terms: Methylene Blue
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention