The Effects Of Parecoxib And Flurbiprofen On Systemic Inflammatory Response Following Cardiopulmonary Bypass

Objective: Cardiopulmonary bypass （CPB） is well known to be associated withsystemic inflammatory response during cardiac surgery. The efficacy of thecyclooxygenase inhibitors parecoxib and flurbiprofen in attenuating this systemicinflammatory response is still unknown.Methods:55Rheumatic heart disease patients undergoing elective mitral valvereplacement with CPB were assessed, enrolled and randomly allocated to3groups:placebo （n=19, given10ml of normal saline at induction of anesthesia,5ml of normalsaline at start of CPB and5ml of normal saline at the end of surgery）, flurbiprofengroup （n=18, given50mg flurbiprofen at induction of anesthesia,25mg flurbiprofen atstart of CPB and25mg flurbiprofen at end of surgery; total flurbiprofen dose of100mg）and parecoxib group （n=18, given40mg parecoxib at induction of anesthesia,20mg parecoxib at start of CPB and20mg parecoxib at end of surgery; total parecoxibdose of80mg）. Blood samples at six different time points （T0-Baseline beforeinduction of anesthesia, T₁-just before start of CPB, T₂-immediately after end ofCPB, T₃-2hrs after end of CPB, T4-24hrs after end of CPB, T5-48hrs after end of CPB.） were collected in EDTA vials for serial measurement of Serum Cytokine levels（IL-6and IL-10）. Duration of ventilation, length of stay in the intensive care unit, andduration of hospital stay after surgery were recorded.Results:（1） Compared to the baseline values at T0, the serum levels of IL-6in thecontrol group increased significantly from T₁–T5, whereas the serum levels of thecytokine remained significantly higher than baseline values at T0in both the parecoxiband flurbiprofen groups at time points T₂-T5. IL-10levels increased significantly in allthe three groups at T₂and T₃. These findings were consistent with the SIRSaccompanying cardiopulmonary bypass.（2） Selective COX-2inhibition by parecoxibresulted in the least rise in IL-6levels at time points T₂and T₃as compared to thecontrol group （at T₂,19.6±8.1pg/ml vs.45.5±10.9pg/ml）（at T₃,31.9±4.8pg/mlvs.77.0±14.1pg/ml, P<0.05）. Peak levels of anti-inflammatory cytokine IL-10occurred immediately after termination of CPB, T₂, and was significantly higher in theparecoxib group （131.7±6.6pg/ml vs.95.4±7.1pg/ml, P<0.05） when compared tothe control group. Flurbiprofen group had no significant changes in levels of IL-6andIL-10as compared to control group. In light of above, parecoxib can more effectivelyattenuate the SIRS associated with cardiopulmonary bypass.（3） There were nosignificant differences among the three groups as regards time till extubation, durationof ICU stay, and length of hospital stay.Conclusion: Intraoperative parecoxib attenuated systemic inflammatory responseassociated with CPB during cardiac surgery while flurbiprofen did not show similarresponse.