Effect of perioperative ketamine on postoperative cognition * a randomized placebo-controlled trial

S(+)-ketamine (ketanestTM) is an N-methyl-D-aspartate receptor (NMDAR)
antagonist available for various indications including the induction and
maintenance of anesthesia (in high dose), perioperative pain relief (in
moderate dose) and chronic pain relief (in low dose). At LUMC perioperative
ketanest is used as adjuvant during large surgical procedures for treatment of
pain and stress (consequently the opioid dose may be reduced) and for reduction
of perioperative inflammation. Worldwide the use of ketamine is rapidly
increasing taking its beneficial effect on chronic pain and ability to produce
a rapid (within hours) onset relief of depression-related symptoms in
therapy-resistant depression.
Both surgery and anesthesia have long-term postoperative effects on cognition.
Especially in the elderly there are indications that stress from surgery (and
hospital admittance) and anesthesia have deleterious effects on postoperative
cognitive dysfunction. Moreover, pain and inflammation may contribute to
postoperative cognitive deterioration. There are indications that ketamine
could improve cognition 1 week following cardiac surgery (Hudetz et al.
Ketamine attenuates post-operative cognitive dysfunction after cardiac surgery.
Acta Anaesthesiol Scand 2009; 53: 864-72). This was related to the
anti-inflammatory effects of ketamine. The current study is aimed at assessing
the effect of ketamine exposure during and following anesthesia on cognition in
patients undergoing elective non-cardiac surgical procedures. To that end
patients will be randomized to receive ketanest or placebo in the peri- and
postoperative phase and cognitive tests will be performed at day 1 and 30
following surgery. Questionnaires will be given on day 1 and day 2
postoperatively, as well as pre-operatively and 30 days after surgery.

We hypothesize that perioperative ketamine will reduce cognitive decline in
postoperative patients, in line with its analgesic and anti-inflammatory
properties. There are no previous data available on the effect of ketamine on
postoperative cognition. We will therefore perform a randomized, double blind,
placebo-controlled trial.

Double blind randomized placebo-controlled

Infusion of s-ketamine

Burden: All patients will be tested at day 0 (day prior to surgery), day 2 and
day 30 after surgery. This will cost the patients 2 additional hours.
Additionally the risk are limited taken the low dose applied.
Benefit: Possibly patients on ketamine will have less cognitive decline and/or
pain in the postoperative period.