Ketamine Attenuates the Interleukin-6 Response After Cardiopulmonary Bypass

Cardiopulmonary bypass (CPB) has been proposed as a model for studying the inflammatory cascade associated with the systemic inflammatory response syndrome.Serum interleukin-6 (IL-6) concentration seems to be a good indicator of activation of the inflammatory cascade and predictor of subsequent organ dysfunction and death. Prolonged increases of circulating IL-6 are associated with morbidity and mortality after cardiac operations. In the present study, we compared the effects of adding ketamine 0.25 mg/kg to general anesthesia on serum IL-6 levels during and after elective coronary artery bypass grafting (CABG). Thirty-one patients undergoing elective CABG were randomized to one of two groups and prospectively studied in a double-blind manner. The patients received either ketamine 0.25 mg/kg or a similar volume of isotonic sodium chloride solution in addition to large-dose fentanyl anesthesia. Blood samples for analysis of serum IL-6 levels were drawn before the operation; after CPB; 4, 24, and 48 h after surgery; and daily for 6 days beginning the third day postoperatively. Ketamine suppressed the serum IL-6 response immediately after CPB and 4, 24, and 48 h postoperatively (P < 0.05). During the first 7 days after surgery, the serum IL-6 levels in the ketamine group were significantly lower than those in the control group (P < 0.05). On Day 8 after surgery, IL-6 levels were no different from baseline values in both groups. A single dose of ketamine 0.25 mg/kg administered before CPB suppresses the increase of serum IL-6 during and after CABG. Implications: In this randomized, double-blind, prospective study of patients during and after coronary artery bypass surgery, we examined whether small-dose ketamine added to general anesthesia before cardiopulmonary bypass suppresses the increase of the serum interleukin-6 (IL-6) concentration. Serum IL-6 levels correlate with the patient's clinical course during and after coronary artery bypass. Ketamine suppresses the increase of serum IL-6 during and after coronary artery bypass surgery. (Anesth Analg 1998;87:266-71)

[1]  B. Barton IL-6: insights into novel biological activities. , 1997, Clinical immunology and immunopathology.

[2]  H. Tilg,et al.  IL-6 and APPs: anti-inflammatory and immunosuppressive mediators. , 1997, Immunology today.

[3]  R. Tompkins The role of proinflammatory cytokines in inflammatory and metabolic responses. , 1997, Annals of surgery.

[4]  G. Hall,et al.  Fentanyl and the interleukin‐6 response to surgery , 1997, Anaesthesia.

[5]  J. Vincent,et al.  Cytokine responses to cardiopulmonary bypass: lessons learned from cardiac transplantation. , 1997, The Annals of thoracic surgery.

[6]  M. Shimaoka,et al.  Ketamine inhibits nitric oxide production in mouse-activated macrophage-like cells. , 1996, British journal of anaesthesia.

[7]  G. Hill The Inflammatory Response to Cardiopulmonary Bypass , 1996, International anesthesiology clinics.

[8]  E. Martin,et al.  Ketamine attenuates endotoxin-induced leukocyte adherence in rat mesenteric venules. , 1995, Critical care medicine.

[9]  M. Entman,et al.  Induction of interleukin-6 synthesis in the myocardium. Potential role in postreperfusion inflammatory injury. , 1995, Circulation.

[10]  L. Greenfield,et al.  Relationship of the proinflammatory cytokines to myocardial ischemia and dysfunction after uncomplicated coronary revascularization. , 1994, The Journal of thoracic and cardiovascular surgery.

[11]  竹中 伊知郎 Ketamine suppresses endotoxin-induced tumor necrosis factor alpha production in mice , 1994 .

[12]  J. Katz,et al.  Postoperative pain: the effect of low-dose ketamine in addition to general anesthesia. , 1993, Anesthesia and analgesia.

[13]  L. Casey Role of cytokines in the pathogenesis of cardiopulmonary-induced multisystem organ failure. , 1993, The Annals of thoracic surgery.

[14]  R. Bone,et al.  Plasma Cytokine and Endotoxin Levels Correlate with Survival in Patients with the Sepsis Syndrome , 1993, Annals of Internal Medicine.

[15]  B. Giroir Mediators of septic shock: New approaches for interrupting the endogenous inflammatory cascade , 1993, Critical care medicine.

[16]  K. Shingu,et al.  Responses of plasma adrenocorticotropic hormone, cortisol, and cytokines during and after upper abdominal surgery. , 1992, Anesthesiology.

[17]  F. Midgley,et al.  Circulating endotoxin and tumor necrosis factor during pediatric cardiac surgery , 1992, Critical care medicine.

[18]  Simon C Watkins,et al.  Negative inotropic effects of cytokines on the heart mediated by nitric oxide. , 1992, Science.

[19]  P. Abbet,et al.  Cytokine production after intravenous or peritoneal gram-negative bacterial challenge in mice. Comparative protective efficacy of antibodies to tumor necrosis factor-alpha and to lipopolysaccharide. , 1992, Journal of immunology.

[20]  A. Dickenson,et al.  The combination of NMDA antagonism and morphine produces profound antinociception in the rat dorsal horn , 1992, Brain Research.

[21]  W. Fraser,et al.  Response of serum interleukin-6 in patients undergoing elective surgery of varying severity. , 1990, Clinical science.

[22]  A. Waage,et al.  Endotoxin, tumor necrosis factor-α and interleukin 1 induce interleukin 6 production in vivo , 1989 .

[23]  Jian-xin Lin,et al.  Stimulation of Interleukin‐6 mRNA Levels by Tumor Necrosis Factor and Interleukin‐1 , 1989 .

[24]  J. Clements,et al.  Pharmacokinetics and analgesic effect of ketamine in man. , 1981, British journal of anaesthesia.