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近年来,随着麻醉技术和心脏外科水平的提高,心脏手术并发症及死亡率明显减少,但心肺转流(CPB)心脏手术常常引起不同程度的脑损伤,严重影响病人的预后,包括脑卒中和亚临床脑损伤[1]。亚临床脑损伤包括无症状脑梗死和术后认知功能障碍。有研究[2]表明,在体外循环心脏手术后,33%~83%的病人会发生术后认知功能障碍。如何加强围手术期脑保护,缩短住院时间,促进病人术后恢复不仅仅是心脏外科医生面临的难题,更是麻醉科医生关注的焦点。盐酸右美托咪定(dexmedetomidine, DEX)是一种高度选择性的α2-肾上腺素能受体激动剂,研究表明DEX可降低交感神经活性,降低脑代谢率,抑制神经细胞凋亡[3];乌司他丁(ulinastatin, UTL)是一种兼有减轻炎症反应和保护器官功能的非特异性蛋白酶抑制剂,可以减轻缺血再灌注损伤。以前的研究[4-5]证实,DEX和UTL单独应用对体外循环下行心脏瓣膜置换术的病人均具有一定脑保护作用,但两种药物联合使用能否发挥协同作用进一步地保护病人的脑功能目前缺乏研究。本研究中将DEX和UTL联合应用于CPB行心脏瓣膜置换术的病人,探讨其脑保护作用,旨在为临床合理用药提供一定的参考。
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选择2020年5月至2021年5月在蚌埠医科大学第一附属医院择期行CPB下瓣膜置换术的心脏瓣膜病病人80例,年龄45~70岁,BMI 18~30 kg/m2, ASAⅡ~Ⅲ级, 无精神病史、听力障碍、语言障碍,左心室射血分数均≥50%,简易智力量表(MMSE)评分>25分,无肝、肾等重要器官功能障碍等。排除标准:(1)急性或进展性心肌梗死、左心室射血分数(LVEF) < 45%的病史;(2)术前有肝肾功能不全、外周血管疾病、糖尿病或动脉高血压病史;(3)术后苏醒拔管延迟及二次剖胸探查止血等病史。该研究由蚌埠医科大学第一附属医院医学研究伦理委员会审查批准(编号2020KY106),病人及家属均签署知情同意书,病人对分组情况并不知情,采用随机数字表法将病人分为4组:0.9%氯化钠溶液组(N组)、DEX组(D组)、UTL组(U组)、DEX联合UTL组(D+U组), 每组20例。4组病人在性别、年龄、BMI、LVEF、体外循环及主动脉阻断时间上比较差异均无统计学意义(P>0.05)(见表 1),具有可比性。
分组 n 男 女 年龄/岁 BMI/(kg/m2) LVEF/% 主动脉阻断时间/min 体外循环时间/min N组 20 11 9 57.2±7.2 23.7±3.7 56.6±3.4 63.4±7.3 98.6±13.5 D组 20 10 10 57.4±6.5 24.5±3.8 56.5±4.3 65.9±9.3 102.8±14.6 U组 20 12 8 56.8±6.8 24.1±3.5 56.1±3.5 66.5±9.5 100.4±14.2 D+U组 20 13 7 58.3±7.5 24.2±3.2 57.4±4.7 65.7±8.6 100.5±15.3 F — 1.02* 0.16 0.17 0.37 0.49 0.29 P — >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 MS组内 — — 49.145 12.655 16.097 75.997 207.785 *示χ2值 表 1 4组病人一般资料的比较(x±s)
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入室后开放静脉,常规监测,同时将脑氧监测传感器置于病人双侧额头以监测脑氧饱和度(rSO2)。给予咪唑安定、依托咪酯、舒芬太尼、罗库溴铵诱导插管,机械通气。全麻后在超声引导下行右侧颈内静脉逆行插管,确保中心静脉导管前端位于颈静脉球部,麻醉维持均采用1%~2%的七氟烷、2~4 mg·kg-1·h-1丙泊酚、8~10 mg/h顺式阿曲库铵和0.4~1.0 μg·kg-1·h-1舒芬太尼维持合理麻醉水平。Narcotrend仪监测麻醉深度,麻醉深度维持在D2~E1水平。术中注意控制输液,可静脉输注晶体液、胶体液及相关血液制品以保持合适的血容量,并适当给予去甲肾上腺素、多巴胺和硝酸甘油等血管活性药物,以纠正病人血流动力学失衡。采用乳酸林格液、复方电解质液等晶体液和血浆、白蛋白等胶体液预充体外循环管道。全部病人均采用提供连续血流的非搏动性体外循环灌注技术,设定泵流量2.0~2.4 L·min-1·m-2,维持平均动脉搏动压在50~ 80 mmHg范围内波动,术中Hct保持在20%以上,根据血气结果维持机体电解质及酸碱平衡[6]。
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D组诱导前开始泵入DEX(江苏恒瑞医药股份有限公司),负荷剂量1.0 μg/kg(设置时间15 min),维持剂量0.4 μg·kg-1·h-1输注, 直至术毕。U组麻醉诱导后即刻静脉注射UTL(天普药业)20 000 U/kg。D+U组2种药物使用方法同上。N组予以等量的0.9%氯化钠溶液。
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(1) 在4组病人麻醉诱导后CPB前(T1)、升主动脉开放(T2)、停机(T3)、术毕6 h(T4)时采集桡动脉和颈静脉球部血各1 mL。用血气分析仪(SIEMENS RAPIDPoint500)测定相关指标如颈内静脉血氧饱和度(SjvO2),按照FICK[7]公式计算出动脉-颈内静脉血氧含量差(Da-jvO2)和脑氧摄取率(CERO2)。脑氧监测仪分别记录4个时间点rSO2,取双侧rSO2平均值。(2)于T1~T4,手术结束24 h(T5)时经右颈内静脉逆行插管采集颈静脉球部血(每个时间点2 mL)。标本收集在普通试管中,室温下用离心机在1 800 g下离心10 min,-70 ℃保存直至分析。根据制造商的说明,使用商用ELISA试剂盒,ELISA法测定血清S-100β蛋白、神经元特异性烯醇化酶(NSE)、白细胞介素-6(IL-6)、肿瘤坏死因子α(TNF-α)的浓度。(3)采用简易智能量表(MMSE) 和意识模糊评估法(CAM)评价4组病人术后1周内的认知功能。术后第7天(T6)时,与术前1 d(T0)相比,MMSE评分越低,表明术后神经认知功能越差。采用CAM法统计术后1周内4组病人谵妄发生的例数[8]。CAM针对谵妄的4个特征分别对应4个条目: ①急性起病或精神状态的波动性改变;②注意力集中困难;③思维混乱;④意识状态的改变。诊断要求必须满足①和②,并且至少满足③或④其中1条。
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采用方差分析、SNK-q检验和χ2检验。
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T1、T4时,4组病人SjvO2、Da-jvO2、CERO2及rSO2差异均无统计学意义(P>0.05)。T2时,与T1相比,4组病人SjvO2显著升高, 而Da-jvO2、CERO2及rSO2显著降低(P < 0.05)。T2~T3时,与N组相比较,D组、U组、D+U组的SjvO2明显升高,Da-jvO2、CERO2明显降低(P < 0.05~P < 0.01);与D组相比,D+U组的SjvO2明显升高,而Da-jvO2、CERO2明显降低(P < 0.01);与U组相比,D+U组的SjvO2明显升高,而Da-jvO2、CERO2明显降低(P < 0.05)。T2时,与N组相比,D组、U组、D+U组的rSO2明显升高(P < 0.01);与D组相比,D+U组的rSO2明显升高(P < 0.05),与U组相比,D+U组的rSO2明显升高(P < 0.05)(见表 2)。
分组 n T1 T2 T3 T4 F P MS组内 SjvO2/% N组 20 65.2±5.6 70.7±5.4▲ 57.5±6.8▲▲▽▽ 65.4±6.0▽▽★★ 16.57 < 0.01 35.743 D组 20 65.6±5.4 78.1±5.9**▲▲ 64.3±6.9*▽▽ 65.1±5.5▽▽ 24.35 < 0.01 35.638 U组 20 65.5±4.3 77.5±7.4**▲▲ 64.0±7.6**▽▽ 65.3±4.5▽▽ 21.13 < 0.01 37.946 D+U组 20 64.2±5.3 83.9±4.8**##▼▼▲▲ 70.8±7.4**##▼▲▽▽ 64.8±6.0▽▽ 43.91 < 0.01 37.567 F — 0.31 16.47 11.40 0.05 — — — P — >0.05 < 0.01 < 0.01 >0.05 — — — MS组内 — 26.775 35.442 51.772 30.570 — — — Da-jvO2/(mmol/L) N组 20 51.4±7.0 35.4±5.6▲▲ 52.4±7.4▽▽ 56.4±7.7▽▽ 35.12 < 0.01 48.780 D组 20 50.2±6.6 26.6±5.8**▲▲ 45.8±6.3**▲▽▽ 55.6±6.6▲▽▽★★ 79.01 < 0.01 40.296 U组 20 50.8±7.2 27.1±6.0**▲▲ 46.6±6.0**▲▽▽ 55.2±7.5▲▽▽★ 67.92 < 0.01 45.193 D+U组 20 49.7±5.9 21.4±6.1**##▼▲▲ 40.0±6.7**##▼▲▲▽ 54.7±6.4▲▽▽** 109.28 < 0.01 39.552 F — 0.24 19.38 11.72 0.20 — — — P — >0.05 < 0.01 < 0.01 >0.05 — — — MS组内 — 45.035 34.605 43.978 50.203 — — — CERO2/% N组 20 37.3±6.2 27.3±5.6▲▲ 41.5±5.6▲▽▽ 40.7±5.7 25.40 < 0.01 33.530 D组 20 35.6±5.9 19.9±5.4**▲▲ 36.0±5.2**▽▽ 40.3±5.9▲★ 50.79 < 0.01 31.573 U组 20 36.3±6.3 20.6±6.2**▲▲ 36.6±6.3**▽▽ 39.6±5.5 39.58 < 0.01 37.170 D+U组 20 34.8±5.4 15.2±4.4**##▼▼▲▲ 31.2±4.7**##▼▼▽▽ 39.4±4.9▲★★ 93.10 < 0.01 23.757 F — 0.63 16.73 11.75 0.24 — — — P — >0.05 < 0.01 < 0.01 >0.05 — — — MS组内 — 35.659 29.669 30.182 30.521 — — — rSO2/% N组 20 74.4±5.2 59.7±5.8▲▲ 70.3±5.5▽▽ 72.5±6.3▽▽ 26.18 < 0.01 32.794 D组 20 74.2±5.1 65.1±5.8**▲▲ 70.6±5.7▽ 72.3±6.4▽▽ 9.17 < 0.01 33.576 U组 20 75.0±5.4 65.0±6.3**▲ 71.1±6.6▽ 72.1±6.2▽ 9.29 < 0.01 37.806 D+U组 20 75.3±5.5 70.3±6.0**#▼▲ 70.5±5.9 73.3±6.7 3.11 < 0.05 36.694 F — 0.18 10.43 0.07 0.13 — — — P — >0.05 < 0.01 >0.05 >0.05 — — — MS组内 — 28.269 35.852 35.603 41.146 — — — 注:与N组比较*P < 0.05,**P < 0.01;与D组比较#P < 0.05,##P < 0.01;与U组比较▼P < 0.05,▼▼P < 0.01;与T1比较▲P < 0.05,▲▲P < 0.01;与T2比较▽P < 0.05,▽▽P < 0.01;与T3比较▽P < 0.05,▽▽P < 0.01;与T4比较★P < 0.05,★★P < 0.01 表 2 4组病人血气指标及rSO2值比较(x±s)
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T1时,4组病人NSE、S-100β蛋白、IL-6及TNF-α水平比较差异均无统计学意义(P>0.05)。T2~T4时,与T1相比,4组病人NSE、S-100蛋白、IL-6及TNF-α水平显著升高(P < 0.01);与N组相比,D组、U组、D+U组的NSE、S-100β、IL-6、TNF-α水平显著降低(P < 0.01);与D组相比,D+U组的NSE、S-100β、IL-6、TNF-α水平显著降低(P < 0.05~P < 0.01);与U组相比,D+U组的NSE、S-100β、IL-6、TNF-α水平显著降低(P < 0.05~P < 0.01)(见表 3)。
分组 n T1 T2 T3 T4 T5 F P MS组内 NSE/(μg/L) N组 20 5.9±2.3 20.6±4.6▲▲ 23.8±4.7▲▲ 27.9±5.8▲▲▽▽△ 9.4±3.2▲▲▽▽△△★★ 96.12 < 0.01 18.600 D组 20 6.4±1.3 16.8±3.5**▲▲ 19.7±4.2**▲▲ 23.2±4.8**▲▲▽▽△ 8.5±3.3▽▽△△★★ 78.86 < 0.01 13.218 U组 20 6.3±1.8 15.7±3.0**▲▲ 18.9±4.5**▲▲ 22.8±5.4**▲▲▽ 8.2±2.8▽▽△△★★ 70.46 < 0.01 13.945 D+U 20 6.1±2.1 12.5±3.2**##▼▼▲▲ 15.1±3.9**##▼▼▲▲▽ 18.1±5.3**##▼▼▲▲▽▽ 7.8±3.2▽▽△△★★ 36.19 < 0.01 13.736 F — 0.26 16.87 13.46 11.18 0.91 — — — P — >0.05 < 0.01 < 0.01 < 0.01 >0.05 — — — MS组内 — 3.719 13.221 18.899 28.680 9.857 — — — S100β/(μg/L) N组 20 0.17±0.04 5.13±1.26▲▲ 5.68±1.15▲▲ 7.24±2.12▲▲△△ 0.42±0.09▽▽△△★★ 140.50 < 0.01 1.484 D组 20 0.18±0.05 3.95±1.15**▲▲ 4.22±1.27*▲▲ 5.72±1.48**▲▲▽△ 0.41±0.10▽▽△△★★ 118.35 < 0.01 1.031 U组 20 0.18±0.04 3.84±1.13**▲▲ 4.40±1.30*▲▲ 5.64±1.59**▲▲▽△ 0.39±0.07▽▽△△★★ 110.27 < 0.01 1.013 D+U 20 0.17±0.06 2.76±1.28**#▼▼▲▲ 3.0±1.27**#▼▲▲ 4.12±1.41**#▼▲▲▽△ 0.37±0.08▽▽△△★★ 58.11 < 0.01 1.052 F — 0.22 12.90 14.27 11.57 1.27 — — — P — >0.05 < 0.01 < 0.01 < 0.01 >0.05 — — — MS组内 — 0.002 1.460 1.563 2.805 0.008 — — — TNF-ɑ/(pg/mL) N组 20 27.6±5.1 65.5±9.8▲▲ 82.2±10.2▲▲▽▽ 58.8±6.7▲▲▽△△ 45.8±6.3▲▲▽▽△△★★ 136.00 < 0.01 62.316 D组 20 26.7±4.4 51.4±8.2**▲▲ 54.3±8.5**▲▲ 43.4±5.9**▲▲▽▽△△ 34.0±5.7**▲▲▽▽△△★★ 59.41 < 0.01 45.349 U组 20 25.6±4.2 44.7±7.6**#▲▲ 50.2±7.9**▲▲▽ 41.3±5.7**▲▲△△ 32.8±5.5**▲▲▽▽△△★★ 47.34 < 0.01 40.239 D+U 20 25.2±4.0 36.4±7.4**##▼▼▲▲ 41.8±7.5**##▼▼▲▲▽ 35.4±5.4**##▼▼▲▲△△ 27.7±5.4**##▼▼▲▲▽▽△△★★ 24.57 < 0.01 37.217 F — 1.19 43.88 83.01 56.09 35.39 — — — P — >0.05 < 0.01 < 0.01 < 0.01 < 0.01 — — — MS组内 — 19.830 69.075 73.865 35.542 33.089 — — — IL-6/(pg/mL) N组 20 65.5±8.7 528.7±46.5▲▲ 642.5±70.5▲▲▽▽ 156.0±36.6▲▲▽▽△△ 60.8±13.5▽▽△△★★ 864.68 < 0.01 1 747.098 D组 20 64.4±8.5 395.3±37.6**▲▲ 452.8±65.4**▲▲▽▽ 124.5±29.7**▲▲▽▽△△ 45.3±11.6**▲▽▽△△★★ 547.89 < 0.01 1 357.119 U组 20 63.2±8.2 363.7±30.3**##▲▲ 396.4±55.5**##▲▲▽▽ 117.8±26.4**▲▲▽▽△△ 38.2±7.8**#▲▲▽▽△△★★ 605.67 < 0.01 965.358 D+U 20 61.4±7.9 286.2±22.4**##▼▼▲▲ 321.5±47.7**##▼▼▲▲▽▽ 95.7±22.5**##▼▼▲▲▽▽ 29.7±5.9**##▼▼▲▲▽▽△△★★ 538.21 < 0.01 676.641 F — 0.88 163.66 102.94 14.49 33.61 — — — P — >0.05 < 0.01 < 0.01 < 0.01 < 0.01 — — — MS组内 69.559 1 250.066 3 652.938 856.843 103.364 — — — 注:与N组比较*P < 0.05,**P < 0.01;与D组比较#P < 0.05,##P < 0.01;与U组比较▼P < 0.05,▼▼P < 0.01;与T1比较▲P < 0.05,▲▲P < 0.01;与T2比较▽P < 0.05,▽▽P < 0.01;与T3比较△P < 0.05,△△P < 0.01;与T4比较★P < 0.05,★★P < 0.01 表 3 4组病人血清中NSE、S-100β、TNF-α、IL-6水平比较(x±s)
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T0时,4组病人MMSE评分比较差异无统计学意义(P>0.05)。T6时,与N组相比,D组、U组、D+U组MMSE评分增高(P < 0.01);与D组相比,D+U组MMSE评分增高(P < 0.01);与U组相比,D+U组MMSE评分增高(P < 0.01)。T6时,与N组相比,D组和U组谵妄发生率差异无统计学意义,而D+U组术后1周内谵妄发生率降低(P < 0.01);与D组相比,D+U组谵妄发生率降低(P < 0.05);与U组相比,D+U组谵妄发生率降低,但差异无统计学意义(P>0.05)(见表 4)。
分组 n T0 T6 术后谵妄(T6) [n;百分率] N组 20 28.5±1.2 23.6±1.4 11(55.00) D组 20 28.6±1.8 25.4±1.3** 7(35.00) U组 20 28.5±1.3 25.3±1.3** 5(25.00) D+U组 20 28.7±1.5 27.2±1.6**##▽▽ 1(5.00) F — 0.09 21.90 12.38▲ P — >0.05 < 0.01 < 0.01 MS组内 — 2.155 1.975 — 注:与N组比较**P < 0.01;与D组比较#P < 0.05,##P < 0.01;与U组比较▽▽P < 0.01;▲示χ2值 表 4 4组病人MMSE评分和谵妄发生率比较(x±s)
右美托咪定联合乌司他丁对心肺转流下瓣膜置换术病人的脑保护作用
Brain protective effect of dexmetomidine combined with ulinastatin on patients undergoing valve replacement under cardiopulmonary bypass
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摘要:
目的研究右美托咪定联合乌司他丁对心肺转流下瓣膜置换术病人的脑保护作用。 方法择期行心脏瓣膜置换术的病人80例,随机分为对照(N)组、右美托咪定(D)组、乌司他丁(U)组、右美托咪定复合乌司他丁(U+D)组。D组病人诱导前予以1.0 μg/kg右美托咪定静脉泵入15 min,之后以0.4 μg·kg-1·h-1持续输注至术毕,U组诱导后给予乌司他丁20 000 U/kg,D+U组右美托咪定和乌司他丁使用方法同上,N组等量0.9%氯化钠溶液。在4组病人体外循环前(T1)、升主动脉开放(T2)、停机(T3)、术毕6 h(T4)行血气分析检测颈内静脉血氧饱和度(SjvO2)、动脉-颈内静脉血氧含量差(Da-jvO2)、脑氧摄取率(CERO2),并记录局部脑氧饱和度(rSO2),同时于T1~T4、术毕24 h(T5)时间点采用ELISA法测定血清白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、S-100β蛋白、神经元特异性烯醇化酶(NSE)含量。最后于术前1 d(T0)、术后第7天(T6)评定术后神经认知,统计术后1周内谵妄的发生情况。 结果T2~T3时,与N组相比,D组、U组、D+U组的SjvO2明显升高,Da-jvO2、CERO2明显降低;与D组、U组相比,D+U组的SjvO2明显升高,而Da-jvO2、CERO2明显降低(P < 0.05~P < 0.01)。T2时,与N组相比,D组、U组、D+U组的rSO2明显升高;与D组、U组相比,D+U组的rSO2明显升高(P < 0.05~P < 0.01)。T2~T4时,与N组相比,D组、U组、D+U组的NSE、S-100β、IL-6、TNF-α水平显著降低;与D组、U组相比,D+U组的NSE、S-100β、IL-6、TNF-α水平显著降低(P < 0.05~P < 0.01)。T6时,与N组相比,D组、U组、D+U组MMSE评分增高;与D组相比,D+U组MMSE评分增高(P < 0.01),与U组相比,D+U组MMSE评分增高,差异有统计学意义(P < 0.01)。T6时,与N组相比,D组和U组谵妄发生率差异无统计学意义,而D+U组术后1周内谵妄发生率降低(P < 0.01);与D组相比,D+U组谵妄发生率降低(P < 0.05)。 结论右美托咪定联合乌司他丁可进一步抑制心瓣膜病病人瓣膜置换手术CPB期间的交感神经活性及炎症反应,显著改善病人围术期脑氧代谢,减轻脑损伤,具有一定的脑保护作用。 Abstract:ObjectiveTo investigate the brain protective effect of dexmedetomidine combined with ulinastatin on patients undergoing valve replacement under cardiopulmonary bypass. MethodsEighty patients undergoing elective cardiac valve replacement were randomly divided into control group (group N), dexmedetomidine group (group D), ulinastatin group (group U), and dexmedetomidine combined with ulinastatin group (group U+D).Group D was pumped 1.0 μg/kg for 15 minutes before induction, and then 0.4 μg·kg-1·h-1 until the end of the operation.Group U was given 20 000 U/kg intravenously immediately after induction.The usage of dexmetomidine and ulinastatin in group U+D was the same as above, and group N had the same amount of 0.9% sodium chloride solution.Before cardiopulmonary bypass (T1), ascending aorta opening (T2), shutdown (T3), and 6 hours after surgery (T4), blood gas analysis was performed to detect internal jugular vein oxygen saturation (SjvO2), arterial internal jugular vein oxygen content difference (Da-jvO2), and cerebral oxygen uptake rate (CERO2) in four groups of patients, and local cerebral oxygen saturation (rSO2) was recorded.Serum interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), S-100 β, and neuron specific enolase (NSE) were measured by ELISA at the time point T1 to T4 and 24 hours after surgery (T5).Finally, postoperative neurocognition was assessed on the first day before surgery (T0) and the seventh day after surgery (T6), and the incidence of delirium within one week after surgery was statistically analyzed. ResultsAt T2-T3, compared with group N, the levels of SjvO2 were remarkably raised in other three groups, while the leves of Da-jvO2 and CERO2 were remarkably descend; compared with group D and group U, the levels of SjvO2 were remarkably raised in group D+U, while the levels of Da-jvO2 and CERO2 was remarkably descend (P < 0.05 to P < 0.01).At T2, compared with group N, the levels of rSO2 was remarkably raised in other three groups; compared with group D and group U, the levels of rSO2 were remarkably raised in group D+U (P < 0.05 to P < 0.01).At T2-T4, compared with group N, the concentration of NSE, S100β, IL-6 and TNF-α was lower in group D, group U and group D+U; compared with group D and group U, the concentration of NSE, S100β, IL-6 and TNF-α was lower in Group D+U (P < 0.05 to P < 0.01).At T6, compared with group N, the MMSE score of others three groups raised; compared with group D, the MMSE score of group D+U increased (P < 0.01), compared with group U, the MMSE score of group D+U increased, there was significant difference (P < 0.01).At T6, compared with group N, there was no significant difference in the incidence of delirium in group D and group U, but the incidence of delirium in group D+U was decreased within one week after operation (P < 0.01), and the incidence of delirium in group D+U was lower than that in group D (P < 0.05). ConclusionsDexmetomidine combined with ulinastatin can further inhibit the sympathetic activity and inflammatory reaction of patients with rheumatic valvular disease during CPB, significantly improve perioperative cerebral oxygen metabolism, reduce brain injury, and have a certain brain protective effect. -
Key words:
- cardiopulmonary bypass /
- valve replacement /
- dexmetomidine /
- ulinastatin /
- brain protection
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表 1 4组病人一般资料的比较(x±s)
分组 n 男 女 年龄/岁 BMI/(kg/m2) LVEF/% 主动脉阻断时间/min 体外循环时间/min N组 20 11 9 57.2±7.2 23.7±3.7 56.6±3.4 63.4±7.3 98.6±13.5 D组 20 10 10 57.4±6.5 24.5±3.8 56.5±4.3 65.9±9.3 102.8±14.6 U组 20 12 8 56.8±6.8 24.1±3.5 56.1±3.5 66.5±9.5 100.4±14.2 D+U组 20 13 7 58.3±7.5 24.2±3.2 57.4±4.7 65.7±8.6 100.5±15.3 F — 1.02* 0.16 0.17 0.37 0.49 0.29 P — >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 MS组内 — — 49.145 12.655 16.097 75.997 207.785 *示χ2值 表 2 4组病人血气指标及rSO2值比较(x±s)
分组 n T1 T2 T3 T4 F P MS组内 SjvO2/% N组 20 65.2±5.6 70.7±5.4▲ 57.5±6.8▲▲▽▽ 65.4±6.0▽▽★★ 16.57 < 0.01 35.743 D组 20 65.6±5.4 78.1±5.9**▲▲ 64.3±6.9*▽▽ 65.1±5.5▽▽ 24.35 < 0.01 35.638 U组 20 65.5±4.3 77.5±7.4**▲▲ 64.0±7.6**▽▽ 65.3±4.5▽▽ 21.13 < 0.01 37.946 D+U组 20 64.2±5.3 83.9±4.8**##▼▼▲▲ 70.8±7.4**##▼▲▽▽ 64.8±6.0▽▽ 43.91 < 0.01 37.567 F — 0.31 16.47 11.40 0.05 — — — P — >0.05 < 0.01 < 0.01 >0.05 — — — MS组内 — 26.775 35.442 51.772 30.570 — — — Da-jvO2/(mmol/L) N组 20 51.4±7.0 35.4±5.6▲▲ 52.4±7.4▽▽ 56.4±7.7▽▽ 35.12 < 0.01 48.780 D组 20 50.2±6.6 26.6±5.8**▲▲ 45.8±6.3**▲▽▽ 55.6±6.6▲▽▽★★ 79.01 < 0.01 40.296 U组 20 50.8±7.2 27.1±6.0**▲▲ 46.6±6.0**▲▽▽ 55.2±7.5▲▽▽★ 67.92 < 0.01 45.193 D+U组 20 49.7±5.9 21.4±6.1**##▼▲▲ 40.0±6.7**##▼▲▲▽ 54.7±6.4▲▽▽** 109.28 < 0.01 39.552 F — 0.24 19.38 11.72 0.20 — — — P — >0.05 < 0.01 < 0.01 >0.05 — — — MS组内 — 45.035 34.605 43.978 50.203 — — — CERO2/% N组 20 37.3±6.2 27.3±5.6▲▲ 41.5±5.6▲▽▽ 40.7±5.7 25.40 < 0.01 33.530 D组 20 35.6±5.9 19.9±5.4**▲▲ 36.0±5.2**▽▽ 40.3±5.9▲★ 50.79 < 0.01 31.573 U组 20 36.3±6.3 20.6±6.2**▲▲ 36.6±6.3**▽▽ 39.6±5.5 39.58 < 0.01 37.170 D+U组 20 34.8±5.4 15.2±4.4**##▼▼▲▲ 31.2±4.7**##▼▼▽▽ 39.4±4.9▲★★ 93.10 < 0.01 23.757 F — 0.63 16.73 11.75 0.24 — — — P — >0.05 < 0.01 < 0.01 >0.05 — — — MS组内 — 35.659 29.669 30.182 30.521 — — — rSO2/% N组 20 74.4±5.2 59.7±5.8▲▲ 70.3±5.5▽▽ 72.5±6.3▽▽ 26.18 < 0.01 32.794 D组 20 74.2±5.1 65.1±5.8**▲▲ 70.6±5.7▽ 72.3±6.4▽▽ 9.17 < 0.01 33.576 U组 20 75.0±5.4 65.0±6.3**▲ 71.1±6.6▽ 72.1±6.2▽ 9.29 < 0.01 37.806 D+U组 20 75.3±5.5 70.3±6.0**#▼▲ 70.5±5.9 73.3±6.7 3.11 < 0.05 36.694 F — 0.18 10.43 0.07 0.13 — — — P — >0.05 < 0.01 >0.05 >0.05 — — — MS组内 — 28.269 35.852 35.603 41.146 — — — 注:与N组比较*P < 0.05,**P < 0.01;与D组比较#P < 0.05,##P < 0.01;与U组比较▼P < 0.05,▼▼P < 0.01;与T1比较▲P < 0.05,▲▲P < 0.01;与T2比较▽P < 0.05,▽▽P < 0.01;与T3比较▽P < 0.05,▽▽P < 0.01;与T4比较★P < 0.05,★★P < 0.01 表 3 4组病人血清中NSE、S-100β、TNF-α、IL-6水平比较(x±s)
分组 n T1 T2 T3 T4 T5 F P MS组内 NSE/(μg/L) N组 20 5.9±2.3 20.6±4.6▲▲ 23.8±4.7▲▲ 27.9±5.8▲▲▽▽△ 9.4±3.2▲▲▽▽△△★★ 96.12 < 0.01 18.600 D组 20 6.4±1.3 16.8±3.5**▲▲ 19.7±4.2**▲▲ 23.2±4.8**▲▲▽▽△ 8.5±3.3▽▽△△★★ 78.86 < 0.01 13.218 U组 20 6.3±1.8 15.7±3.0**▲▲ 18.9±4.5**▲▲ 22.8±5.4**▲▲▽ 8.2±2.8▽▽△△★★ 70.46 < 0.01 13.945 D+U 20 6.1±2.1 12.5±3.2**##▼▼▲▲ 15.1±3.9**##▼▼▲▲▽ 18.1±5.3**##▼▼▲▲▽▽ 7.8±3.2▽▽△△★★ 36.19 < 0.01 13.736 F — 0.26 16.87 13.46 11.18 0.91 — — — P — >0.05 < 0.01 < 0.01 < 0.01 >0.05 — — — MS组内 — 3.719 13.221 18.899 28.680 9.857 — — — S100β/(μg/L) N组 20 0.17±0.04 5.13±1.26▲▲ 5.68±1.15▲▲ 7.24±2.12▲▲△△ 0.42±0.09▽▽△△★★ 140.50 < 0.01 1.484 D组 20 0.18±0.05 3.95±1.15**▲▲ 4.22±1.27*▲▲ 5.72±1.48**▲▲▽△ 0.41±0.10▽▽△△★★ 118.35 < 0.01 1.031 U组 20 0.18±0.04 3.84±1.13**▲▲ 4.40±1.30*▲▲ 5.64±1.59**▲▲▽△ 0.39±0.07▽▽△△★★ 110.27 < 0.01 1.013 D+U 20 0.17±0.06 2.76±1.28**#▼▼▲▲ 3.0±1.27**#▼▲▲ 4.12±1.41**#▼▲▲▽△ 0.37±0.08▽▽△△★★ 58.11 < 0.01 1.052 F — 0.22 12.90 14.27 11.57 1.27 — — — P — >0.05 < 0.01 < 0.01 < 0.01 >0.05 — — — MS组内 — 0.002 1.460 1.563 2.805 0.008 — — — TNF-ɑ/(pg/mL) N组 20 27.6±5.1 65.5±9.8▲▲ 82.2±10.2▲▲▽▽ 58.8±6.7▲▲▽△△ 45.8±6.3▲▲▽▽△△★★ 136.00 < 0.01 62.316 D组 20 26.7±4.4 51.4±8.2**▲▲ 54.3±8.5**▲▲ 43.4±5.9**▲▲▽▽△△ 34.0±5.7**▲▲▽▽△△★★ 59.41 < 0.01 45.349 U组 20 25.6±4.2 44.7±7.6**#▲▲ 50.2±7.9**▲▲▽ 41.3±5.7**▲▲△△ 32.8±5.5**▲▲▽▽△△★★ 47.34 < 0.01 40.239 D+U 20 25.2±4.0 36.4±7.4**##▼▼▲▲ 41.8±7.5**##▼▼▲▲▽ 35.4±5.4**##▼▼▲▲△△ 27.7±5.4**##▼▼▲▲▽▽△△★★ 24.57 < 0.01 37.217 F — 1.19 43.88 83.01 56.09 35.39 — — — P — >0.05 < 0.01 < 0.01 < 0.01 < 0.01 — — — MS组内 — 19.830 69.075 73.865 35.542 33.089 — — — IL-6/(pg/mL) N组 20 65.5±8.7 528.7±46.5▲▲ 642.5±70.5▲▲▽▽ 156.0±36.6▲▲▽▽△△ 60.8±13.5▽▽△△★★ 864.68 < 0.01 1 747.098 D组 20 64.4±8.5 395.3±37.6**▲▲ 452.8±65.4**▲▲▽▽ 124.5±29.7**▲▲▽▽△△ 45.3±11.6**▲▽▽△△★★ 547.89 < 0.01 1 357.119 U组 20 63.2±8.2 363.7±30.3**##▲▲ 396.4±55.5**##▲▲▽▽ 117.8±26.4**▲▲▽▽△△ 38.2±7.8**#▲▲▽▽△△★★ 605.67 < 0.01 965.358 D+U 20 61.4±7.9 286.2±22.4**##▼▼▲▲ 321.5±47.7**##▼▼▲▲▽▽ 95.7±22.5**##▼▼▲▲▽▽ 29.7±5.9**##▼▼▲▲▽▽△△★★ 538.21 < 0.01 676.641 F — 0.88 163.66 102.94 14.49 33.61 — — — P — >0.05 < 0.01 < 0.01 < 0.01 < 0.01 — — — MS组内 69.559 1 250.066 3 652.938 856.843 103.364 — — — 注:与N组比较*P < 0.05,**P < 0.01;与D组比较#P < 0.05,##P < 0.01;与U组比较▼P < 0.05,▼▼P < 0.01;与T1比较▲P < 0.05,▲▲P < 0.01;与T2比较▽P < 0.05,▽▽P < 0.01;与T3比较△P < 0.05,△△P < 0.01;与T4比较★P < 0.05,★★P < 0.01 表 4 4组病人MMSE评分和谵妄发生率比较(x±s)
分组 n T0 T6 术后谵妄(T6) [n;百分率] N组 20 28.5±1.2 23.6±1.4 11(55.00) D组 20 28.6±1.8 25.4±1.3** 7(35.00) U组 20 28.5±1.3 25.3±1.3** 5(25.00) D+U组 20 28.7±1.5 27.2±1.6**##▽▽ 1(5.00) F — 0.09 21.90 12.38▲ P — >0.05 < 0.01 < 0.01 MS组内 — 2.155 1.975 — 注:与N组比较**P < 0.01;与D组比较#P < 0.05,##P < 0.01;与U组比较▽▽P < 0.01;▲示χ2值 -
[1] INDJA B, WOLDENDORP K, VALLELY MP, et al. Silent brain infarcts following cardiac procedures: a systematic review and meta-analysis[J]. J Am Heart Assoc, 2019, 8(9): e010920. doi: 10.1161/JAHA.118.010920 [2] KUMPAITIENE B, SVAGZDIENE M, SIRVINSKAS E, et al. Cerebrovascular autoregulation impairments during cardiac surgery with cardiopulmonary bypass are related to postoperative cognitive deterioration: prospective observational study[J]. Minerva Anestesiol, 2019, 85(6): 594. [3] BAO N, TANG B. Organ-protective effects and the underlying mechanism of dexmedetomidine[J]. Mediators Inflamm, 2020, 2020(1): 1. [4] GONG J, ZHANG R, SHEN L, et al. The brain protective effect of dexmedetomidine during surgery for paediatric patients with congenital heart disease[J]. J Int Med Res, 2019, 47(4): 1677. doi: 10.1177/0300060518821272 [5] 石林玉, 张莉, 金恒芳, 等. 患儿法洛四联症矫治术中乌司他丁对脑损伤S100β蛋白和神经元特异性烯醇化酶的影响[J]. 临床麻醉学杂志, 2018, 34(10): 984. [6] 张娜, 刘金东. 体外循环心脏手术脑损伤及脑保护的研究进展[J]. 中华麻醉学杂志, 2020, 40(1): 120. [7] 李超, 田首元, 刘淑芳, 等. 极小潮气量机械通气在输尿管软镜手术中的应用[J]. 临床麻醉学杂志, 2020, 36(8): 779. [8] 郭宗锋, 王祥, 曹苏, 等. 右美托咪定联合乌司他丁对行腹腔镜下结直肠癌手术的老年患者围术期神经认知障碍的影响——多中心、随机、双盲、对照研究[J]. 中国全科医学, 2020, 23(36): 4578. [9] CHEN Y, ZHANG X, ZHANG B, et al. Dexmedetomidine reduces the neuronal apoptosis related to cardiopulmonary bypass by inhibiting activation of the JAK2-STAT3 pathway[J]. Drug Des Devel Ther, 2017, 11: 2787. doi: 10.2147/DDDT.S140644 [10] KAMENSHCHIKOV NO, MANDEL IA, PODOKSENOV YK, et al. Nitric oxide provides myocardial protection when added to the cardiopulmonary bypass circuit during cardiac surgery: Randomized trial[J]. J Thorac Cardiovasc Surg, 2019, 157(6): 2328. doi: 10.1016/j.jtcvs.2018.08.117 [11] 刘超, 刘锴, 罗纲, 等. 右美托咪定对心脏瓣膜置换术者围术期的神经保护作用及认知水平的影响[J]. 中国临床研究, 2020, 33(7): 913. [12] 闵祥振, 贾智勇, 郭蕊, 等. 近红外光谱脑氧饱和度监测的临床应用进展[J]. 临床麻醉学杂志, 2020, 36(3): 307. [13] KUMPAITIENE B, SVAGZDIENE M, DRIGOTIENE I, et al. Correlation among decreased regional cerebral oxygen saturation, blood levels of brain injury biomarkers, and cognitive disorder[J]. J Int Med Res, 2018, 46(9): 3621. doi: 10.1177/0300060518776545 [14] 王龙. 乌司他丁对体外循环心脏手术患者心脏炎症状态的影响[J]. 天津医科大学学报, 2017, 23(5): 446. [15] XIONG J, QUAN J, QIN C, et al. Dexmedetomidine exerts brain-protective effects under cardiopulmonary bypass through inhibiting the janus kinase 2/signal transducers and activators of transcription 3 pathway[J]. J Interferon Cytokine Res, 2020, 40(2): 116. doi: 10.1089/jir.2019.0110 [16] LIM H, KIM TY, KIM SY, et al. The protective effects of dexmedetomidine preconditioning on hepatic ischemia/reperfusion injury in rats[J]. Transplant Proc, 2021, 53(1): 427. doi: 10.1016/j.transproceed.2020.10.014 [17] LIU Y, WANG YL, ZOU SH, et al. Effect of high-dose ulinastatin on the cardiopulmonary bypass-induced inflammatory response in patients undergoing open-heart surgery[J]. Chin Med J (Engl), 2020, 133(12): 1476. doi: 10.1097/CM9.0000000000000832