Ketamine attenuates post-operative cognitive dysfunction after cardiac surgery.
BACKGROUND
Post-operative cognitive dysfunction (POCD) commonly occurs after cardiac surgery. Ketamine exerts neuroprotective effects after cerebral ischemia by anti-excitotoxic and anti-inflammatory mechanisms. We hypothesized that ketamine attenuates POCD in patients undergoing cardiac surgery concomitant with an anti-inflammatory effect.


METHODS
Patients randomly received placebo (0.9% saline; n=26) or an i.v. bolus of ketamine (0.5 mg/kg; n=26) during anesthetic induction. Anesthesia was maintained with isoflurane and fentanyl. A nonsurgical group (n=26) was also included as control. Recent verbal and nonverbal memory and executive functions were assessed before and 1 week after surgery or a 1-week waiting period for the nonsurgical controls. Serum C-reactive protein (CRP) concentrations were determined before surgery and on the first post-operative day.


RESULTS
Baseline neurocognitive and depression scores were similar in the placebo, ketamine, and nonsurgical control groups. Cognitive performance after surgery decreased by at least 2 SDs (z-score of 1.96) in 21 patients in the placebo group and only in seven patients in the ketamine group compared with the nonsurgical controls (P<0.001, Fisher's exact test). Cognitive performance was also significantly different between the placebo- and the ketamine-treated groups based on all z-scores (P<0.001, Mann-Whitney U-test). Pre-operative CRP concentrations were similar (P<0.33, Mann-Whitney U-test) in the placebo- and ketamine-treated groups. The post-operative CRP concentration was significantly (P<0.01, Mann-Whitney U-test) lower in the ketamine-treated than in the placebo-treated group.


CONCLUSIONS
Ketamine attenuates POCD 1 week after cardiac surgery and this effect may be related to the anti-inflammatory action of the drug.
Department of Anesthesiology, Clement J. Zablocki Veterans Administration Medical Center, Milwaukee, WI. judith.hudetz@va.gov
J A
JA
Hudetz
Z
Z
Iqbal
S D
SD
Gandhi
K M
KM
Patterson
A J
AJ
Byrne
A G
AG
Hudetz
P S
PS
Pagel
D C
DC
Warltier
D000368:Aged; D000768:Anesthesia, General; D000778:Anesthetics, Dissociative / Q000627:therapeutic use*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D002097:C-Reactive Protein / Q000032:analysis; D006348:Cardiac Surgical Procedures; D003072:Cognition Disorders / Q000517:prevention & control* / Q000523:psychology*; D003863:Depression / Q000209:etiology / Q000523:psychology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007649:Ketamine / Q000627:therapeutic use*; D008297:Male; D008568:Memory / Q000187:drug effects; D008875:Middle Aged; D018696:Neuroprotective Agents / Q000494:pharmacology; D009483:Neuropsychological Tests; D011183:Postoperative Complications / Q000517:prevention & control* / Q000523:psychology*; D012086:Reoperation
D000778:Anesthetics, Dissociative; D000894:Anti-Inflammatory Agents, Non-Steroidal; D018696:Neuroprotective Agents; D007649:Ketamine; D002097:C-Reactive Protein