Effects Of Ulinastatin On Inflammatory Cytokines Levels And Respiratory Index In Patients Undergoing CPB And Correlation Between Them

Background and Objective:Cardiopulmonary bypass is an important method during open heart operation.Along with the improvement of CPB devices,myocardial preservation and cardiac surgery technique,the complication and fatality rate have been decreased significantly.But pulmonary injury is still one of the main complications during cardio- pulmonary bypass.In fact,the pulmonary function is damaged in nearly almost patients undergoing cardiopulmonary bypass.In some serious case,it will become acute respiratory distress syndrome.As a result,the fatality rate is very high.The reason of pulmonary injury during cardiopulmonary bypass is multifactorial.And the inflammatory reaction in the lung play an important role during pulmonary injury of CPB.The activated neutrophilic granulocyte during CPB release inflammatory factors such as elastase and interleukin-8.These inflammatory factors stay at the lung and damage the the pulmonary function.Until now there are still no ideal drugs for pulmonary injury of CPB.The purpose of this essay is to investigate the effects of ulinastatin on pro-and anti-inflammatory cytokines and respiratory index during open heart surgery under CPB.Methods:Sixty ASAⅡ-Ⅲpatients of either sex(27males , 33 females)scheduled for elective valve replacement under CPB were randomly divided into two groups of 30 each: control group(C)and ulinastatin group (W).Patients with hepato-renal dysfunction or taking glucocorticoid were excluded.The patients were premedicated with intramuscular phenobarbital 0.1g and Scopolamine0.3mg . Anesthesia was induced with midazolam 0.1mg/kg , fentanyl 10μg/kg and vecuronium 0.1mg/kg . After tracheal intubation aesthesia was maintained with midazolam and fentanyl . The patients were mechanically ventilated.VT was set at 8-12 ml/kg,RR10-12 bpm and I:E=1:2.PETCO2 was maintained at 35-45 mg.In ulinastatin group,the patients received ulinastatin 12 000 U/kg of which half was given i.v. before CPB and half was added to the priming fluid,while group C received normal saline instead of ulinastatin.Blood samples were taken from radial artery for determination of plasma TNF-a,IL-6,and IL-10 concentrations and blood gas analysis before operation(T1),30 min after initiation of CPB(T2),1 h(T3),4 h(T4)and 24 h(T5) after CPB.Respiratory index (PA-aDO2/PaO2) was calculated at Tl-5.Results:There were no significant differences in sex,age,weight,height,duration of CPB,and aortic cross-clamping time between the two groups.1.In group C the plasma levels of TNF-a,IL-6 and IL-10 were significantly higher than the baseline values(T1) during and after CPB (P<0.01).2.In group W the plasma levels of TNF-a,IL-6 and IL-10 did not increase until T3 and returned to baseline levels (TNF-a, IL-6) or were greatly decreased (IL-10) at T5.The plasma TNF-a and IL-6 concentrations were significantly higher while the plasma IL-10 concentration was significantly lower in group C than in group W after CPB(P<0.01).3.The TNF-a/IL-10 ratio and IL-6/IL-10 ratio were significantly higher in group C than in group W after CPB(P<0.01) . 4.The respiratory index in control group was significantly higher than the baseline(T1) and that in group W after CPB (P<0.01 or 0.05).Plasma IL-10 concentration and respiratory index were positively correlated with plasma concentration of TNF-a and IL-6 whereas respiratory index was negatively correlated with the plasma IL-10 level.Conclusion : Cardiopulmonary bypass induced serious lung injury characterized by increased levels of TNF-αand interleukin-6.Our results show that ulinastatin can effectively adjust the balance between pro- and anti-inflammatory cytokines and protect respiratory function.The lung function was significantly improved in patients on ulinastatin administration.