Post Operative Cognitive Dysfunction Clinical Trial
The Prevention of Post Operative Cognitive Dysfunction by Ketamine: a Prospective Multicenter Randomized Blinded Placebo-controlled Trial in Elderly Patients Undergoing Elective Orthopaedic Surgery
Postoperative delirium is a frequent complication of major surgery and affects 10% to 70% of
surgical patients > 60 years. Delirium is associated with increased morbidity and mortality,
prolonged recovery, functional and cognitive dysfunction with nursing home or long-term care
facility placement. The acute deterioration in cognition and psychomotor agitation
frequently seen with delirium is often distressing for both patients and their relatives.
The pathophysiology and causal relationship between delirium and persistent postoperative
cognitive dysfunction remain incompletely understood. Identified clinical risk factors for
both include advanced age, type of surgery, preexisting cognitive impairment, and drug
addiction. The inflammatory response triggered by surgical trauma and pain may contribute to
the development of delirium and cognitive impairment after surgery.
Ketamine, a N-methyl-D-aspartic acid receptor antagonist, is commonly used in anaesthesia and postoperative analgesia. By reducing both pain and glutamate excitotoxic effects on neuronal and microglial brain cells, it contributes to tone down the neuroinflammatory process associated with surgery. A recent body of evidence has shown that ketamine reduces the depressive-like behavior induced by inflammatory or stress-induced stimuli in mice. Ketamine was also found to reduce by 28% the absolute risk of postoperative delirium and levels of inflammatory biomarkers in cardiac surgical patients.
Orthopaedic surgery is a high-risk situation for developing postoperative delirium. In patients undergoing total hip or knee replacement, the prevalence (incidence, respectively) of delirium is 17% (12-51%, respectively) and it is associated with a 6-fold increase increased risk of developing dementia and cognitive dysfunction after surgery. Hundred thousands of patients > 60 years undergo elective orthopaedic procedures per year around the world. The purpose of the study is to assess the superiority of ketamine at subanaesthetic dose versus placebo to reduce the incidence of postoperative delirium in patients aged ≥ 60 years undergoing elective orthopaedic surgery under general anaesthesia.
The design consists in a prospective multicenter randomized blinded placebo-controlled trial
in elderly patients undergoing elective orthopaedic surgery.
Patients will be informed at the pre-anaesthetic consultation, 7 to 30 days before surgery. They will be randomized the day before surgery. Cognitive and depressive status at baseline will be assessed precisely the day pior to surgery with cognitive tests. Self-administered scores will be recorded to evaluate depression, anxiety, and quality of life.
At the day of surgery, patients in the experimental group will receive a bolus of low intravenous dose (sub-anaesthetic) 0.5 mg/kg ketamine following induction of anaesthesia. Patients in the control group will receive a bolus of an intravenous normal saline solution following induction of anaesthesia.
From D0 (2 hours after surgery end) to D7 or discharge from the hospital if earlier, delirium, pain, adverse clinical and psychiatric events will be measured and recorded.
Cognitive functions, neuropathic pain, depression, anxiety and quality of life will be assessed at D7 or discharge from the hospital if earlier and D90.
Inflammatory markers will be measured before surgery, at D1, D7 or discharge from the hospital if earlier and D90. ;
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention
|Source||Assistance Publique - Hôpitaux de Paris|
|Contact||Jean Mantz, MD, PhD|
|Status||Not yet recruiting|
|Start date||October 2016|
|Completion date||February 2019|
|Enrolling by invitation||
||Phase 1/Phase 2|
|Not yet recruiting||