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Ketamine and the coagulation response during and after cardiopulmonary bypass.

INTRODUCTION. The inflammatory response and the coagulation-fibrinolytic cascades are closely interconnected. Vascular injury following cardiopulmonary bypass (CPB) may result in uncontrolled platelet activation, thrombin generation, and disseminated intravacular coagulation. Many of the anesthetic agents posses immunomodulatory effects. The clinical implications of such effects in the context of CPB remain unknown. Ketamine attenuates IL-6 response and production of the superoxide anion by neutrophils after CPB, and reduces coronary uptake of neutrophils following myocardial ishemia and reperfusion. We studied the effect of small dose ketamine on the coagulation response (antithrombin III, fibrinogen, D-dimers, platelets) during and after CPB. METHODS. In the preliminary prospective study report, we randomized 30 patients underwent open heart surgery in two groups: K-group (n=15), which received 0, 5 mg/kg ketamine, and P-group (n=15), which received placebo. Serum samples were collected before starting operation (T0), after aorta clamp releasing (T1), 30 min (T2), 2 (T3), 6 (T4), 12 (T5), 24 (T6), and 48 hours (T7) after weaning from CPB. Data (mean± ; SD) were done by variance analysis. RESULTS. Both group were comparable for age, sex, and body surface area. Differences of operative (CPB and aorta cross- clamping time), and postoperative date (ventilatory support, ICU stay, blood transfusion) between groups were not significant. Parameters Measurement T0 T1 T2 T3 T4 T5 T6 T7 CRP(mg/dl) K 3.6± ; 2.9 2.0± ; 1.6 2.6± ; 1.8 2.6± ; 2.1 8.4± ; 5.6 33.2± ; 17.0 104.7± ; 35.7 122.2± ; 53.3 P 5.0± ; 5.6 4.1± ; 5.6 4.1± ; 6.1 4.5± ; 6.9 11.5± ; 10.1 36.3± ; 18.3 102.9± ; 38.8 121.2± ; 52.3 WBC (x103) K 4.7± ; 1.4*‡ 8.3± ; 3.1 11.0± ; 2.4 11.4± ; 3.1 11.2± ; 3.6 10.1± ; 2.7 11.8± ; 2.9 10.9± ; 4.5 P 7.0± ; 3.1 8.9± ; 4.7 12.4± ; 3.9 12.3± ; 3.3 11.5± ; 3.0 10.1± ; 3.0 10.6± ; 2.9 8.7± ; 3.5 PMN (x103) K 3.1± ; 1.4 5.9± ; 2.8 9.1± ; 2.1 9.3± ; 2.7 9.7± ; 3.2 9.2± ; 3.1 10.3± ; 3.6 9.1± ; 4.1 P 4.5± ; 2.0 6.1± ; 3.1 10.1± ; 3.4 10.0± ; 2.4 9.9± ; 2.5 8.4± ; 2.1 8.7± ; 2.5 10.2± ; 8.7 Htc (%) K 0.35± ; 0.1 0.21± ; 0.0 0.29± ; 0.2 0.32± ; 0.2 0.33± ; 0.1 0.34± ; 0.2 0.34± ; 0.1 0.29± ; 0.3 P 0.40± ; 0.0 0.22± ; 0.0 0.30± ; 0.4 0.32± ; 0.3 0.33± ; 0.2 0.32± ; 0.3 0.33± ; 0.1 0.30± ; 0.1 Lactate (mmol/l) K 1.0± ; 0.1 2.1± ; 0.5 2.6± ; 0.6 2.5± ; 0.7 2.9± ; 1.0 2.5± ; 0.8 1.7± ; 0.8 1.1± ; 0.4 P 1.1± ; 0.3 2.0± ; 0.4 2.1± ; 0.3 2.1± ; 0.4 2.3± ; 0.8 2.0± ; 1.0 1.3± ; 0.5 1.1± ; 0.4 AT III (%) K 80.0± ; 9.5 50.9± ; 5.4 55.5± ; 7.8 57.4± ; 9.7 65.3± ; 12.4 66.5± ; 9.0 67.7± ; 5.6 67.9± ; 7.9 P 86.6± ; 14.8 57.3± ; 9.3 58.0± ; 14.0 71.3± ; 15.6 73.8± ; 10.8 75.0± ; 9.3 74.0± ; 10.2 72.7± ; 11.9 fibrinogen (g/L) K 3.3± ; 0.7 1.9± ; 0.3 2.0± ; 0.3 2.2± ; 0.3 2.4± ; 0.4 2.7± ; 0.5 3.6± ; 1.1 4.3± ; 1.5 P 3.3± ; 0.9 2.0± ; 0.4 2.2± ; 0.8 2.4± ; 0.4 2.7± ; 0.4 3.0± ; 0.5 4.3± ; 1.2 5.3± ; 1.3 D-dimers ( g/mL) K 0.3± ; 0.1 1.8± ; 1.3 2.9± ; 1.8 2.8± ; 1.7 2.5± ; 1.3 2.1± ; 1.3 1.6± ; 1.1 0.7± ; 0.2 P 0.5± ; 0.6 1.8± ; 1.5 3.3± ; 2.4 2.9± ; 2.3 2.1± ; 1.4 1.6± ; 0.9 1.4± ; 1.1 1.1± ; 0.9 Platelets (x103) K 173.0± ; 48.3 116.1± ; 39.9 99.7± ; 25.8 109.1± ; 32.6 117.0± ; 37.3 102.9± ; 39.3 96.2± ; 32.6 85.5± ; 23.4 P 170.1± ; 67.5 133.7± ; 56.9 100.1± ; 41.6 126.3± ; 44.8 145.5± ; 40.7 133.4± ; 38.7 121.2± ; 41.9 107.1± ; 44.4 *p<0.05 between groups ; ‡ p<0.05 within groups ; (K = ketamine group, P = placebo group) CONCLUSION. In this preliminary study, findings suggest that small doses of ketamine posses any effect on the coagulation response during and after CPB.

coagulation; inflammation; cardiac surgery

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