艾司氯胺酮对儿童活体肝移植受者炎症因子及心肌损伤标志物的影响

Effect of esketamine on inflammatory cytokines and myocardial injury markers in pediatric patients undergoing living-donor liver transplantation

目的探索艾司氯胺酮对儿童肝移植受者炎症因子及心肌损伤标志物的影响。方法随机对照临床研究。选择2022年7月至2022年12月天津市第一中心医院收治的拟行活体肝移植术的胆道闭锁患儿50例。采用随机数字表法将其分为艾司氯胺酮组(E组,25例)和对照组(C组,25例)。E组儿童肝移植受者麻醉诱导时给予艾司氯胺酮0.5 mg/kg,麻醉诱导后以0.5 mg·kg-1·h-1剂量持续泵注艾司氯胺酮直至术毕。C组麻醉诱导及维持阶段使用相同剂量0.9%氯化钠注射液作为空白对照。记录两组受者的基本信息及诱导后5 min(T0)、无肝期30 min(T1)、新肝开放即刻(T2)、新肝期30 min(T3)、术毕(T4)时间点的心率、平均动脉压(mean arterial pressure,MAP)和中心静脉压;于T0、T1、T3、T4时采集中心静脉血样,检测血清心肌肌钙蛋白I(cardiac troponin I,cTnI)、肌酸激酶同工酶MB(creatine kinase isoenzyme-MB,CK-MB)、肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)和白细胞介素-6(interleukin-6,IL-6)浓度。记录受者心脏不良事件的发生例数、术后机械通气时间、重症监护室停留时间及住院时间。组间比较采用独立样本t检验,组内各时点比较采用重复测量方差分析;非正态分布的计量资料以M(IQR)表示,组间比较采用非参数检验。结果C组和E组受者T2时的MAP分别为(39.3±8.0)mmHg(1 mmHg=0.133 kPa)和(48.6±12.7)mmHg,较T0时的(53.2±9.4)mmHg和(55.6±10.7)mmHg低,差异均有统计学意义(P值均<0.001);C组和E组T3时间点炎症因子TNF-α和IL-6浓度分别为169.0(207.1)ng/L和(132.63±51.75)ng/L、78.5(138.8)ng/L和(87.44±32.17)ng/L,分别较C组和E组T0时间点的43.8(26.4)ng/L和(51.79±17.83)ng/L、54.2(63.1)ng/L和(60.54±20.75)ng/L高,差异均有统计学意义(P值均<0.001)。C组T3、T4时间点心肌损伤标志物CK-MB和cTnI浓度分别较T0时间点升高[T3比T0:5.7(5.4)μg/L比4.0(3.5)μg/L,0.09(0.08)μg/L比0.02(0.02)μg/L;T4比T0:5.3(5.0)μg/L比4.0(3.5)μg/L,0.07(0.08)μg/L比0.02(0.02)μg/L],差异均有统计学意义(P值均<0.001)。E组T3、T4时间点CK-MB和cTnI浓度分别较T0时间点升高[7.1(5.0)μg/L比4.6(2.1)μg/L,0.06(0.09)μg/L比0.03(0.04)μg/L;5.4(4.9)μg/L比4.6(2.1)μg/L,0.03(0.06)μg/L比0.03(0.04)μg/L],差异均有统计学意义(P值均<0.001)。与C组比较,E组T1、T2、T3时间点MAP升高[(58.8±10.3)mmHg比(53.3±8.6)mmHg;(48.6±12.7)mmHg比(39.3±8.0)mmHg;(55.8±7.4)mmHg比(51.5±7.3)mmHg],差异均有统计学意义(P=0.048,0.003和0.044);与C组比较,E组T3、T4时TNF-α和IL-6浓度均出现降低[T3:78.5(138.8)ng/L比169.0(207.1)ng/L,(87.44±32.17)ng/L比(132.63±51.75)ng/L;T4:62.3(118.3)ng/L比141.3(129.2)ng/L,(74.34±26.38)ng/L比(100.59±30.40)ng/L],差异均有统计学意义(P=0.010、0.017、0.001和0.002);与C组比较,E组T3、T4时cTnI浓度均降低[0.06(0.09)μg/L比0.09(0.08)μg/L;0.03(0.06)μg/L比0.07(0.08)μg/L],差异均有统计学意义(P=0.014和0.003)。与C组比较,E组机械通气时间减少[195(120)min比315(239)min],差异有统计学意义(P<0.001);与C组比较,E组严重低血压、心动过缓、心肌缺血和室性早搏发生率均降低[16%(4/25)比48%(12/25);12%(3/25)比36%(9/25);4%(1/25)比24%(6/25);0比4%(1/25)],差异均有统计学意义(P=0.015、0.047、0.042、0.312)。结论术中给予艾司氯胺酮能够减轻儿童肝移植受者全身炎症反应,有利于减轻围手术期心肌损伤。

Objective To explore the effect of esketamine on inflammatory cytokines and myocardial injury markers in children undergoing living-donor liver transplantation(LT).Methods Considering the inclusion criteria,50 children with biliary atresia were selected for living donor LT.They were equally randomized into two groups of control(C)and esketamine(E)(25 cases each).Esketamine 0.5 mg/kg was administered to group E during induction and continued at a dose of 0.5 mg·kg–1·h-1 after an induction of anesthesia.Group C provided the same dose of 0.9%sodium chloride injection during induction and then continued to pumping until the end of the procedure.Basic profiles of two groups were recorded.Hemodynamic parameters,such as heart rate(HR),mean arterial pressure(MAP)and central venous pressure(CVP),were monitored at 5 min of anesthesia induction(T0),30 min of anhepatic phase(T1),immediately after repercussion(T2),30 min of neohepatic phase(T3)and end of surgery(T4)in both groups.Central venous blood samples were collected at T0,T1,T3 and T4.Serum levels of cardiac troponin I(cTnI),creatine kinase isoenzyme-MB(CK-MB),tumor necrosis factor alpha(TNF-α)and interleukin-6(IL-6)were measured.The incidence of adverse cardiac events,postoperative mechanical ventilation time,ICU stay and hospitalization length were compared.Results As compared with T0,mean arterial pressure(MAP)at T2 declined markedly in group E[(48.6±12.7)mmHg(1 mmHg=0.133 kPa)vs(55.6±10.7)mmHg,P<0.001]and C[(39.3±8.0)mmHg vs(53.2±9.4)mmHg,P<0.001];As compared with T0,the TNF-αand IL-6 spiked at T3 in group C[169.0(207.1)ng/L vs 43.8(26.4)ng/L,(132.63±51.75)ng/L vs(51.79±17.83)ng/L,P<0.001]and E[78.5(138.8)ng/L vs 43.8(26.4)ng/L,(87.44±32.17)ng/L vs(51.79±17.83)ng/L,P<0.001];In group C,the concentration of myocardial injury markers CK-MB and cTnI rose at T3/T4 compared with T0[T3 vs T0:5.7(5.4)μg/L vs 4.0(3.5)μg/L,0.09(0.08)μg/L vs 0.02(0.02)μg/L;T4 vs T0:5.3(5.0)μg/L vs 4.0(3.5)μg/L,0.07(0.08)μg/L vs 0.02(0.02)μg/L,P<0.001].In group E,the levels of CK-MB and cTnI were higher at T3/T4 than those at T0[T3 vs T0:7.0(5.0)μg/L vs 4.6(2.1)μg/L,0.06(0.09)μg/L vs 0.03(0.04)μg/L;T4 vs T0:5.4(4.9)μg/L vs 4.6(2.1)μg/L,0.03(0.06)μg/L vs 0.03(0.04)μg/L;P<0.001].Compared with group C,the MAP of E rose at T1/T2/T3[(58.8±10.3)mmHg vs(53.3±8.6)mmHg,P=0.048;(48.6±12.7)mmHg vs(39.3±8.0)mmHg,P=0.003;(55.8±7.4)mmHg vs(51.5±7.3)mmHg,P=0.044].Compared with group C,TNF-αand IL-6 decreased in E at T3/T4[T3:78.5(138.8)ng/L vs 169.0(207.1)ng/L,P=0.010;(87.44±32.17)ng/L vs(132.63±51.75)ng/L,P=0.017.T4:62.3(118.3)ng/L vs 141.3(129.2)ng/L,P=0.001;(74.34±26.38)ng/L vs(100.59±30.40)ng/L,P=0.002].Compared with group C,cTnI decreased in E at T3/T4[0.06(0.09)μg/L vs 0.09(0.08)μg/L,P=0.014;0.03(0.06)μg/L vs 0.07(0.08)μg/L,P=0.003].Compared with group C,the mechanical ventilation time in group E decreased[195(120)min vs 315(239)min,P<0.001].Compared with group C,the incidence of severe hypotension[16%(4/25)vs 48%(12/25),P=0.015],bradycardia[12%(3/25)vs 36%(9/25),P=0.047],myocardial ischemia[4%(1/25)vs 24%(6/25),P=0.042]and premature ventricular contractions[0 vs 4%(1/25),P=0.312]decreased in group E.Conclusion Intraoperative dosing of esketamine may suppress inflammatory reactions and alleviate perioperative myocardial injury in children undergoing living-donor LT.