摘要：
目的 评价重组人促红细胞生成素(rHuEPO)对体外循环心脏瓣膜置换术患者脑损伤的影响.方法 择期拟行体外循环心脏瓣膜置换术的慢性瓣膜性心脏病患者45例,年龄36～ 62岁,体重42～ 92 kg,ASA分级Ⅱ或Ⅲ级,心功能分级Ⅱ或Ⅲ级,采用随机数字表法分为3组(n=15):对照组(C组)和不同剂量rHuEPO组(EPO1组和EPO2组).EPO1组于麻醉诱导前静脉注射rHuEPO40 IU/kg;EPO2组于麻醉诱导前静脉注射rHuEP0 80 IU/kg.分别于麻醉诱导前(T0,基础值)、气管插管后即刻(T1)、主动脉插管即刻(T2)、上下腔静脉插管即刻(T3)、CPB开始即刻(T4)、CPB中各指标最低值(T5)、复温至36.5°C(T6)、CPB停机即刻(T7)和停机后1 h(T8)时,记录双侧额叶脑氧饱和度(rSO2)、组织血红蛋白指数(THI)、氧合血红蛋白浓度变化(△O2Hb)、还原血红蛋白浓度变化(△HHb)和总血红蛋白浓度变化(△cHb);记录rSO2最低值≤50％和rSO2最低值较基础值降低幅度(△rSO2)≥20％的发生情况.分别于T0、T8和CPB停机后2 h(T9)时,采集静脉血样,采用ELISA法测定血清S100蛋白和神经元特异性烯醇化酶(NSE)的浓度.分别于术前1d和术后8d时采用简易精神状况检查法、数字广度试验、符号-数字模式测验、连线测验A型和Stroop字色干扰效应试验评估认知功能,记录术后认知功能障碍的发生情况.分别于术前1d和术后8d时,行自评抑郁量表评分和自评焦虑量表评分.结果 3组间各时点双侧rSO2、双侧△cHb、双侧rSO2最低值≤50％和术后认知功能障碍的发生率、自评抑郁量表评分和自评焦虑量表评分比较差异无统计学意义(P＞0.05).与C组比较,EPO1组左侧△rSO2≥20％的发生率降低,T6,8时右侧△O2Hb升高,T9时血清NSE浓度降低,T8时血清S100蛋白浓度降低,术后8d时符号-数字模式测验完成个数增加,EPO2组T2、T3、T5、T7和T8时右侧THI降低,T2和T3时右侧△HHb升高,术后8d时Stroop字色干扰B完成时间缩短(P＜0.05或0.01);与EPO1组比较,EP02组左侧△rSO2≥20％的发生率升高,T2-4和T6-8时右侧THI降低,T6,7时左侧△O2Hb和T8时右侧△O2Hb降低(P＜0.05).结论 麻醉诱导前静脉注射rHuEPO40 IU/kg可减轻体外循环心脏瓣膜置换术患者脑损伤.%Objective To evaluate the effect of recombinant human erythropoietin (rHuEPO) on brain injury in the patients undergoing cardiac valve replacement with cardiopulmonary bypass (CPB).Methods Forty-five patients with chronic valvular heart disease,aged 36-62 yr,weighing 42-92 kg,of American Society of Anesthesiologists physical status Ⅱ or Ⅲ,with New York Heart Association of Ⅱ or Ⅲ,undergoing cardiac valve replacement with CPB,were randomly divided into 3 groups (n =15 each) using a random number table:control group (group C),and different doses of rHuEPO groups (EPO1 group,EPO2 group).In EPO1 and EPO2 groups,rHuEPO 40 and 80 IU/kg were injected intravenously before anesthesia induction,respectively.Before anesthesia induction (T0,baseline value),immediately after endotracheal intubation (T1),immediately after aortic cannulation (T2),immediately after cannulation of superior and inferior vena cava (T3),immediately after the beginning of CPB (T4),when each index was decreased to the minimal value during CPB (T5),after rewarming to 36.5 °C (T6),immediately after termination of CPB (T7),and at 1 h after termination of CPB (T8),regional cerebral oxygen saturation (rSO2),tissue hemoglobin index (THI),and changes in concentrations of oxyhemoglobin (△ O2Hb),deoxyhemoglobin (△ HHb) and total hemoglobin (△ cHb) in bilateral frontal lobes were recorded.The patients whose minimal rSO2 ≤ 50％ and decrease in minimal rSO2 ≥ 20％ of the baseline value (△rSO2) were recorded.At T0,T8 and 2 h after termination of CPB (T9),venous blood samples were taken for determination of serum concentrations of S100 protein and neuron-specific enolase (NSE) by ELISA.At 1 day before surgery and 8 days after surgery,the patient's cognitive function was assessed using Mini-Mental State Examination,the Digit Span subtest of the Wechsler Adult Intelligence Scale-Revised (WAIS-R),the Digit Symbol subtest of the WAIS-R,the Trailing Making Test (Part A)and the Stroop Color Word Interference Test,while depression and anxiety were assessed by Zung Self-Rating Depression Scale and Zung Self-Rating Anxiety Scale,respectively.The occurrence of postoperative cognitive dysfunction was recorded.Results There was no significant difference among the three groups in bilateral rSO2 and △ cHb,incidence of bilateral rSO2 ≤ 50％ and postoperative cognitive dysfunction,Zung Self-Rating Depression Scale score,and Zung Self-Rating anxiety Scale score at each time point (P＞0.05).Compared with group C,the incidence of left △ rSO2 ≥ 20％ was significantly decreased,the right △ O2 Hb was increased at T6,8,the serum NSE concentrations were decreased at T9,the serum S100 protein concentrations were decreased at T8,and the number of the Digit Symbol subtest of the WAIS-R completed was increased in group EPO1,and right THI was significantly decreased at T2,T3,T5,T7 and T8,right △ HHb was increased at T2 and T3,and the completion time of Stroop color word interference test B was shortened at 8 days after surgery in group EPO2 (P＜0.05 or 0.01).Compared with group EPO1,the incidence of left △rSO2 ≥ 20％ was significantly increased,the right THI was decreased at T2-4 and T6-8,and the left △ O2 Hb at T6-7 and right △ O2 Hb at T8 were decreased in group EPO2 (P＜0.05).Conclusion rHuEPO 40 IU/kg injected intravenously before induction of anesthesia can mitigate brain injury in the patients undergoing cardiac valve replacement with CPB.
