Ketamine attenuates neutrophil activation after cardiopulmonary bypass.
Surgery is associated with activation of neutrophils and their influx into affected tissue. The pathogenic role of superoxide production generated by activated neutrophils has been documented repeatedly. Ketamine suppresses neutrophil oxygen radical production in vitro. In the present study, we compared the effect of adding small-dose ketamine to opioids during the induction of general anesthesia on superoxide production by neutrophils after coronary artery bypass grafting (CABG). Thirty-five patients undergoing elective CABG were randomized to one of two groups and prospectively studied in a double-blinded manner. The patients received either ketamine 0.25 mg/kg or a similar volume of saline in addition to large-dose fentanyl anesthesia. Blood samples were drawn before the operation, immediately after cardiopulmonary bypass, 24 and 48 postoperative h, and on postoperative Days 3-6. Functional capacity of neutrophils was assessed by superoxide generation after stimulation with phorbol 12-myristate 13-acetate, opsonized zymosan, or formyl-methionyl-leucyl-phenylalanine. The addition of small-dose ketamine to general anesthesia attenuates increased production of the superoxide anion (O2-) by neutrophils without chemical stimulation and after stimulation with phorbol 12-myristate 13-acetate, formyl-methionyl-leucyl-phenylalanine, and opsonized zymosan for 4-6 days after CABG. In addition, ketamine attenuated the percentage of neutrophils on postoperative Days 2-6. In the Control group, superoxide production significantly increased compared with the baseline value. By contrast, in the Ketamine group, this difference was not significant.


CONCLUSIONS
In a randomized, double-blinded, prospective clinical study, we compared the effect of adding small-dose ketamine to opioids during general anesthesia on superoxide production and showed that ketamine suppressed the increase of superoxide anion production by neutrophils after coronary artery bypass grafting.
Division of Anesthesiology, Soroka Medical Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 84101, Israel.
Genadi
G
Zilberstein
Rachel
R
Levy
Maxim
M
Rachinsky
Allan
A
Fisher
Lev
L
Greemberg
Yoram
Y
Shapira
Azai
A
Appelbaum
Leonid
L
Roytblat
D000368:Aged; D000768:Anesthesia, General; D000778:Anesthetics, Dissociative; D018686:Anesthetics, Intravenous; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D001026:Coronary Artery Bypass / Q000009:adverse effects; D004311:Double-Blind Method; D005260:Female; D005283:Fentanyl; D006801:Humans; D007649:Ketamine; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D009240:N-Formylmethionine Leucyl-Phenylalanine; D018375:Neutrophil Activation / Q000187:drug effects*; D011183:Postoperative Complications / Q000097:blood*; D011446:Prospective Studies; D013481:Superoxides / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate
D000778:Anesthetics, Dissociative; D018686:Anesthetics, Intravenous; D013481:Superoxides; D009240:N-Formylmethionine Leucyl-Phenylalanine; D007649:Ketamine; D013755:Tetradecanoylphorbol Acetate; D005283:Fentanyl