Ketamine and Postoperative Cognitive Dysfunction

Summary

Over 30 million patients require a major surgery annually in the US alone and more than half of them are performed in patients over 60 years of age. Post-operative cognitive dysfunction (POCD) is a keystone complication of these surgeries and affects up to 40% of surgical patients aged over 60 years on discharge from the hospital. Despite controlled longitudinal studies have shown that POCD is transient, it is associated with delirium, higher mortality, earlier retirement, and greater utilization of social financial assistance The pathophysiology of persistent postoperative cognitive dysfunction and causal relationship between POCD and delirium remain incompletely understood. Identified clinical risk factors for both include advanced age, type of surgery, preexisting cognitive impairment, and drug addiction. We and others have provided evidence that 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 levels of inflammatory biomarkers in cardiac surgical patients.

Orthopaedic surgery is a high-risk situation for developing postoperative cognitive dysfunction. In patients undergoing non-cardiac surgery, the prevalence of POCD is 26% one week after surgery and decreased to 10% at 3 months postoperatively, and a similar prevalence is found 12 months after the operation. Postoperative delirium is associated with an increased risk of POCD. Hundred thousands of patients \> 60 years undergo elective orthopaedic procedures per year around the world.

Conditions

• Post Operative Cognitive Dysfunction

Interventions

DRUG

Ketamine

A bolus of low intravenous dose (sub-anaesthetic) 0.5 mg/kg ketamine following induction of anaesthesia.

DRUG

Placebo

A bolus of an intravenous normal saline solution following induction of anaesthesia.

Sponsors & Collaborators

• Ministry of Health, France

  collaborator OTHER_GOV

• Assistance Publique - Hôpitaux de Paris

  lead OTHER

Principal Investigators

• Franck Verdonk, MD, PhD · Assistance Publique - Hôpitaux de Paris

Study Design

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

60 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2017-03-20

Primary Completion

2019-08-31

Completion

2019-08-31

Countries

• France

Study Locations