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.