• 中国科技论文统计源期刊
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Volume 44 Issue 5
May  2019
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Value of GDFT guided by TEE combined with small dose of norepinephrine in the application of laparoscopic colorectal cancer surgery in elderly patients

  • Corresponding author: ZHENG Li-dong, zld801@163.com
  • Received Date: 2018-10-22
    Accepted Date: 2019-03-18
  • ObjectiveTo observe the effects of goal-directed fluid therapy(GDFT) guided by transesophageal echocardiography(TEE) combined with small dose of norepinephrine on intraoperative circulation management and postoperative recovery in elderly patients treated with laparoscopic colorectal surgery.MethodsFifty patients over 60 years scheduled by radical resection of colorectal cancer, ASA grade Ⅰto Ⅱ, were randomly divided into the observation group and control group(25 cases each group).The observation group was treated with GDFT guided by TEE combined with small doses of norepinephrine, and the control group was treated with conventional liquid.The amounts of liquid and norepinephrine in observation group after anesthesia were adjusted according to the blood flow time corrected(FTc) and stroke volume(SV) of the descending aorta monitored by TEE, and the control group was treated with the traditional method fluid infusion.The mean artery pressure(MAP), heart rate(HR) and central venous pressure(CVP) between two groups were compared before anesthesia induction(T0) and tracheal intubation(T1), at the time of establishing artificial pneumoperitoneum(T2), after resecting tumor(T3), after stopping pneumoperitoneum(T4) and after extubation(T5).The crystal/gel ratio and total amount, urine volume, levels of aspertate aminotransferase(AST), alanine aminotransferase(ALT), blood urea nitrogen(BUN) and creatinine(Cr), and incidence rates of adverse reaction and complications during postoperative recovery were recorded in two groups.ResultsThe amounts of intraoperative urine and balance solution infusion in observation group were significantly less than those in control group(P < 0.01 and P < 0.05), and the amount of polygelatin peptide infusion in observation group was significantly more than that in control group(P < 0.05).The HR and MAP in two groups at T1 and T2 decreased compared with at T0(P < 0.05 to P < 0.01), and the CVP in two groups at T1 increased compared with at T0(P < 0.01).Compared with the control group, the HR in observation group increased at T4 and T5(P < 0.01), and the CVP in observation group decreased at T3, T4 and T5(P < 0.01).Compared with before operation, the ALT level increased, and the levels of AST and BUN decreased in observation group after operation(P < 0.01).The differences of the levels of ALT, AST, BUN and Cr in control group were not statistically significantly between before and after operation(P>0.05).There was no statistical significance in the incidence rate of adverse reaction between observation group(16.0%) and contorl group(28.0%), and the incidence rate of complications in observation group(8.0%) was significantly lower than that in control group(32.0%)(P < 0.05).ConclusionsThe GDFT guided by TEE combined with small dose of norepinephrine has advantages in the postoperative recovery of patients treated with laparoscopic colorectal surgery.
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  • [1] 王天龙.目标导向液体治疗在围术期的应用[J].北京医学, 2014, (8):620. doi: 10.3969/j.issn.0253-9713.2014.08.003
    [2] 解雅英, 于建设, 丁翠霞, 等.食管超声多普勒监测仪指导下目标导向液体治疗在大肠癌手术应用的临床观察[J].国际麻醉学与复苏杂志, 2014, 35(12):1085. doi: 10.3760/cma.j.issn.1673-4378.2014.12.005
    [3] 中华医学会麻醉学分会α1激动剂围术期应用专家组.α1肾上腺素能受体激动剂围术期应用专家共识(2017版)[J].临床麻醉学杂志, 2017, 33(2):186.
    [4] 米勒.米勒麻醉学[M].北京:北京大学医学出版社, 2006:25.
    [5] ABBAS SM, HILL AG.Systematic review of the literature for the use of oesophageal Doppler monitor for fluid replacement in major abdominal surgery[J].Anaesthesia, 2008, 63(1):44.
    [6] DINDO D, EDMARTINES N, CLAVIEN PA.Classification of surgical complications:a new proposal with evaluation in a cohort of 6336 patients and results of a survey[J].Ann Surg, 2004, 240(2):205. doi: 10.1097/01.sla.0000133083.54934.ae
    [7] GITZELMANN CA, MENDOZA-SAGAON M, TALAMINI MA, et al.Cell-mediated immune response is better preserved by laparoscopy than laparotomy[J].Surgery, 2000, 127(1):65. doi: 10.1067/msy.2000.101152
    [8] PENG H, ZHANG J, CAI C, et al.The Influence of carbon dioxide pneumoperitoneum on systemic inflammatory response syndrome and bacterial translocation in patients with bacterial peritonitis caused by acute appendicitis[J].Surg Innov, 2018, 25(1):7.
    [9] MYLES PS, BELLOMO R, CORCORAN T, et al.Restrictive versus liberal fluid therapy for major abdominal surgery[J].N Engl J Med, 2018, 378(24):2263. doi: 10.1056/NEJMoa1801601
    [10] FUTIER E, LEFRANT JY, GUINOT PG, et al.Effect of individualized vs standard blood pressure management strategies on postoperative organ dysfunction among high-risk patients undergoing major surgery:a randomized clinical trial[J].JAMA, 2017, 318(14):1346. doi: 10.1001/jama.2017.14172
    [11] ROLLINS KE, LOBO DN.Intraoperative goal-directed fluid therapy in elective major abdominal surgery:a meta-analysis of randomized controlled trials[J].Ann Surg, 2016, 263(3):465. doi: 10.1097/SLA.0000000000001366
    [12] GIRAUDO G, BRACHET CONTUL R, CACCETTA M, et al.Gasless laparoscopy could avoid alterations in hepatic function[J].Surg Endosc, 2001, 15(7):741. doi: 10.1007/s004640090020
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Value of GDFT guided by TEE combined with small dose of norepinephrine in the application of laparoscopic colorectal cancer surgery in elderly patients

    Corresponding author: ZHENG Li-dong, zld801@163.com
  • Department of Anesthesiology, The People's Hospital of Lu'an, Lu'an Anhui 237000, China

Abstract: ObjectiveTo observe the effects of goal-directed fluid therapy(GDFT) guided by transesophageal echocardiography(TEE) combined with small dose of norepinephrine on intraoperative circulation management and postoperative recovery in elderly patients treated with laparoscopic colorectal surgery.MethodsFifty patients over 60 years scheduled by radical resection of colorectal cancer, ASA grade Ⅰto Ⅱ, were randomly divided into the observation group and control group(25 cases each group).The observation group was treated with GDFT guided by TEE combined with small doses of norepinephrine, and the control group was treated with conventional liquid.The amounts of liquid and norepinephrine in observation group after anesthesia were adjusted according to the blood flow time corrected(FTc) and stroke volume(SV) of the descending aorta monitored by TEE, and the control group was treated with the traditional method fluid infusion.The mean artery pressure(MAP), heart rate(HR) and central venous pressure(CVP) between two groups were compared before anesthesia induction(T0) and tracheal intubation(T1), at the time of establishing artificial pneumoperitoneum(T2), after resecting tumor(T3), after stopping pneumoperitoneum(T4) and after extubation(T5).The crystal/gel ratio and total amount, urine volume, levels of aspertate aminotransferase(AST), alanine aminotransferase(ALT), blood urea nitrogen(BUN) and creatinine(Cr), and incidence rates of adverse reaction and complications during postoperative recovery were recorded in two groups.ResultsThe amounts of intraoperative urine and balance solution infusion in observation group were significantly less than those in control group(P < 0.01 and P < 0.05), and the amount of polygelatin peptide infusion in observation group was significantly more than that in control group(P < 0.05).The HR and MAP in two groups at T1 and T2 decreased compared with at T0(P < 0.05 to P < 0.01), and the CVP in two groups at T1 increased compared with at T0(P < 0.01).Compared with the control group, the HR in observation group increased at T4 and T5(P < 0.01), and the CVP in observation group decreased at T3, T4 and T5(P < 0.01).Compared with before operation, the ALT level increased, and the levels of AST and BUN decreased in observation group after operation(P < 0.01).The differences of the levels of ALT, AST, BUN and Cr in control group were not statistically significantly between before and after operation(P>0.05).There was no statistical significance in the incidence rate of adverse reaction between observation group(16.0%) and contorl group(28.0%), and the incidence rate of complications in observation group(8.0%) was significantly lower than that in control group(32.0%)(P < 0.05).ConclusionsThe GDFT guided by TEE combined with small dose of norepinephrine has advantages in the postoperative recovery of patients treated with laparoscopic colorectal surgery.

  • 近年来经食管超声心动图(transesophageal echocardiography,TEE)以其实时、准确、无创、快捷的优势,广泛应用于指导术中目标导向液体治疗(goal-directed fluid therapy,GDFT),进而改善病人术后的转归[1-2]。除容量对血压的影响,全身麻醉后容量血管扩张所导致的回心血量减少也是术中低血压的一个重要原因,大部分麻醉药物具有负性肌力作用并可引起血管扩张。在麻醉状态下,血管的容积会大大增加。单纯靠补充液体来维持正常生理状态,即使有GDFT作为指导,手术病人也极有可能会输入比正常生理状态更多的液体。去甲肾上腺素可收缩血管,对抗麻醉药物所致的扩血管不良反应,配合适当的容量治疗后,可补充因麻醉药引起的相对性循环容量不足,从而维持重要器官血流灌注,减少对输液的过度依赖[3]。本文旨在探讨经TEE为导向的GDFT联合小剂量去甲肾上腺素用于老年腹腔镜结直肠手术与传统补液方法的比较, 通过观察病人术后重要脏器相关检查指标及不良反应和并发症情况,为临床麻醉提供参考。

1.   资料与方法
  • 择期行乙状结肠或直肠癌根治术的病人50例,ASA麻醉分级Ⅰ~Ⅱ级,无严重心肝肾疾病,无食管病变或食管手术史等TEE使用禁忌证,年龄60岁以上,体质量45~80 kg,男女不限。随机分为2组,每组25例,其中观察组为TEE指导下GDFT联合小剂量去甲肾上腺素组(N组),对照组为常规液体治疗组(C组)。本研究经我院伦理委员会批准,告知病人及家属相关监测项目内容,取得同意后并签署知情同意书。

  • 所有病人均不给予术前用药。病人入室后均于局麻下行桡动脉穿刺监测有创动脉压(invasive arterial blood pressure,IABP)、心电图、脉搏血氧饱和度、麻醉深度监测系统Narcotrend (NT指数)。建立静脉通路后依次缓慢注射给予咪达唑仑0.03 mg/kg、舒芬太尼0.8~1.0 μg/kg、依托咪酯0.2~0.4 mg/kg。病人意识消失后,静脉推注罗库溴铵0.8~1.2 mg/kg。待肌松充分后行气管内插管,设定通气参数为潮气量8~10 mL/kg、呼吸频率12~18次/分。N组于气管插管后经口置入美国GE公司Vivid E95型TEE探头,深度距离门齿距离为25~30 cm,并调整图像至最佳。麻醉维持期采用丙泊酚靶控输注,血浆靶浓度为3~6 μg/mL,维持NT指数E0~D1。术中间断推注罗库溴铵0.2~0.3 mg/kg维持肌松,根据血气分析等检测数据调整呼吸参数并维持呼气末二氧化碳分压于35~45 mmHg。2组病人均于气管插管后行右颈内静脉穿刺置管监测中心静脉压(central venous pressure,CVP),术中2组病人都给予保温毯保温并维持体温于36.0~37.0 ℃。术后2组均给予静脉自控镇痛。

  • C组容量管理方案:依据传统的补液经验公式“输入液体总量=补偿性扩容量+生理需要量+累计缺失量+继续损失量+第三间隙丢失量”[4];其中补偿性扩容量用聚明胶肽6~8 mL/kg计算,继续损失量按失血量计算并以聚明胶肽补充,生理需要量与累计缺失量根据4-2-1法则以平衡液补充,第三间隙丢失量以平衡液5 mL/kg计算。补偿性扩容量于麻醉诱导前补充, 其余液体于术中补充。C组病人术中平均动脉压(mean arterial pressure,MAP) < 65 mmHg超过2 min时给予静脉推注盐酸麻黄碱注射液3~10 mg,并维持MAP的波动在基础血压的20%以内。

    N组容量管理方案:诱导期输注平衡液量4~6 mL·kg-1·h-1同时微泵输注去甲肾上腺素, 起始泵注速度为0.05 μg·kg-1·min-1,术中调整其泵注的速度上限为0.1 μg·kg-1·min-1。插管后根据TEE监测降主动脉的纠正血流时间(flow time corrected,FTc)和每搏输出量(stroke volume,SV)调整聚明胶肽的输注量[5]或去甲肾上腺素的泵注速度。具体方法为:如果FTc < 350 ms或SV减少>10%,则在15 min内输注聚明胶肽3 mL/kg; 如果FTc>350 ms但SV增加>10%以上, 继续输注聚明胶肽3 mL/kg直至SV维持稳定;如果SV稳定,但是FTc < 350 ms则调整去甲肾上腺素的泵注速度直至FTc>350 ms,以上操作步骤中的参数每隔20 min记录一次。2组均根据术中血气分析和出血量决定是否需要成分输血并调整电解质平衡,维持病人内环境稳定。

  • 记录2组病人麻醉诱导前(T0)、气管插管前(T1)、建立人工气腹后即刻(T2)、肿物切除(T3)、停止气腹后(T4)、拔管后(T5)的MAP、心率(heart rate,HR)、CVP、晶体/胶体比例及总量,术毕尿量。并通过观察病人术后的肝肾功能检查指标包括天门冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)、血浆尿素氮(BUN)、肌酐(Cr)、术后恢复期不良反应和并发症情况来评估病人住院期间的转归。

  • 采用t(或t′)检验、方差分析、q检验和χ2检验。

2.   结果
  • 2组病人性别、年龄、体质量指数(BMI)、人工气腹时间、失血量及NT值差异均无统计学意义(P>0.05)(见表 1)。

    分组 n 年龄/岁 BMI/(kg/m2) 人工气腹时间/min 失血量/mL NT值
    N组 25 19 5 68±6 21.9±1.9 132±34 330±22 35±10
    C组 25 21 4 66±4 22.1±1.7 139±30 310±31 37±8
    t 0.19* 1.39 0.39 0.77 2.63 0.78
    P >0.05 >0.05 >0.05 >0.05 < 0.05 >0.05
    *示χ2
  • N组术中尿量、平衡液输注量明显少于C组(P<0.01和P<0.05),聚明胶肽输注量多于C组(P<0.05)(见表 2)。2组病人HR、MAP在T1、T2时间点均较麻醉诱导前T0时间点降低(P < 0.05~P < 0.01),CVP在T1时间点较T0时间点增高(P < 0.01)。与C组比较,N组HR在T4、T5时间点升高(P < 0.01),CVP在T3、T4、T5时间点降低(P < 0.01),MAP在各时间点差异均无统计学意义(P>0.05)(见表 3)。

    分组 n 尿量 平衡液 聚明胶肽 总量
    N组 25 610±33 1631±834 955±526 2586±1360
    C组 25 815±40 2107±1014 638±412 2745±1426
    t 19.77 2.04 2.37 0.40
    P < 0.01 < 0.05 < 0.05 >0.05
    分组 T0 T1 T2 T3 T4 T5 F P MS组内
    HR/(次/分)
      N组 78±10 67±4** 67±9** 76±9 76±4 71±4** 359.21 < 0.01 51.667
      C组 81±9 69±3** 67±8** 78±4 72±3** 67±6** 24.47 < 0.01 35.833
        t 1.11 2.00 0.00 1.02 4.00 2.77
        P >0.05 >0.05 >0.05 >0.05 < 0.01 < 0.01
    CVP/mmHg
      N组 5.20±1.23 9.15±0.26** 6.45±1.21** 7.67±1.24** 8.70±1.45** 9.91±0.46** 68.17 < 0.01 1.149
      C组 4.83±1.64 8.80±0.32** 5.62±1.33** 10.64±1.50** 11.52±1.33** 12.71±1.24** 153.17 < 0.01 1.686
        t 0.90 4.24 2.31 7.63 7.17 10.59
        P >0.05 < 0.01 < 0.05 < 0.01 < 0.01 < 0.01
    MAP/mmHg
      N组 81±8 63±5** 57±5** 89±34 91±23 90±21 14.83 < 0.01 373.333
      C组 84±3 65±4* 58±6** 83±34 89±32 87±34 7.34 < 0.01 566.167
        t 1.76 1.56 0.64 0.62 0.25 0.38
        P >0.05 >0.05 >0.05 >0.05 >0.05 >0.05
    q检验:与T0时间点比较*P < 0.05, **P < 0.01
  • 术前,N组ALT水平高于C组(P < 0.01),其他指标在2组间差异均无统计学意义(P>0.05);与术前比较,术后N组的ALT水平升高(P < 0.01),AST和BUN水平下降(P < 0.01),Cr差异无统计学意义(P>0.05);与术前比较,术后C组的ALT、AST、BUN、Cr差异均无统计学意义(P>0.05)(见表 4)。

    分组 n ALT/(U/L) AST/(U/L) BUN/(mmol/L) Cr/(mmol/L)
    术前
      N组 25 12.0±5.1 19.7±4.2 5.8±1.0 65.1±17.0
      C组 25 20.1±8.4 21.3±15.5 5.5±1.8 67.2±11.2
        t 4.12 0.49 0.73 0.52
        P < 0.01 >0.05 >0.05 >0.05
    术后
      N组 25 18.5±8.3** 14.4±4.7** 3.9±1.4** 63.5±16.1
      C组 25 16.2±4.1 19.7±5.1 5.9±1.3 68.4±10.7
        t 1.24 3.82 5.23 1.27
        P >0.05 < 0.01 < 0.01 >0.05
    △示t′值; 与术前比较**P < 0.01
  • 本研究中病人术后不良反应主要包括恶心呕吐和谵妄,C组发生恶心呕吐6例、谵妄1例,N组发生恶心呕吐4例、谵妄无;术后并发症主要包括切口感染、切口裂开、肺部感染、非计划转入ICU,C组以上并发症分别发生1、1、5、1例,N组分别发生1、0、1、0例。N组不良反应发生率16.0%(4/25)与C组不良反应发生率28.0%(7/25)差异无统计学意义(χ2=1.05,P>0.05),N组并发症发生率8.0%(2/25)明显低于C组并发症发生率32.0%(8/25)(χ2=4.50,P < 0.05)。

3.   讨论
  • 腹腔镜结直肠手术虽然有手术创伤小、病人术后胃肠道功能恢复快等优势[7]。但是手术时程、气腹时间的长短以及手术医生的操作熟练程度等因素对病人术中内环境的影响不亚于开腹手术[8],这也给术中容量管理带来困难。开放的补液方式下病人往往在术中输入过多的液体,在麻醉状态结束后,一旦病人的血管张力开始恢复,过多的补液会造成容量过负荷,势必会造成部分液体进入人体中压力较低的部位如肺脏、胃肠道、第三间隙等。这样就容易引起手术后肺、胃肠道黏膜水肿等问题,进而影响预后。然而限制性的容量管理又会造成术后肾损伤的发生率,且不改善腹部手术病人的术后转归[9]。因此,针对不同的病人制定个体化管理才能降低术后器官功能不全的风险[10],从而改善病人的转归。GDFT虽然是目前公认的个体化容量管理方案,但是用于其管理的指标和方法众多,这也导致了争议的存在。最近的Meta分析[11]表明GDFT在减少总体并发症发生率、住院时间、ICU驻留时间上有优势,本研究部分观察指标也支持这一结果。分析中还显示出病人短期死亡率、肛门排气时间、术后肠麻痹发生上无显著性差异,并且快速康复外科管理的腹部大手术病人没有受益。这提示我们GDFT并不完美,还需要更多的研究去充实它。

    本研究的理论基础:术中补充容量的主要目的是维持血压接近病人的基础血压,在决定血压的因素中,除了心脏的泵功能,另一个重要因素即心脏后负荷。对一个正常的病人来说,术中短时间内影响血压的主要因素是容量和血管张力,要维持血流动力学稳定,维持满意的机体灌注状态,应该是液体输注为基础并结合血管活性药物的合理使用。在实验中小剂量的去甲肾上腺素可以预防全麻诱导时的血压剧烈波动,术中通过FTc和SV为指标能快速识别术中病人前负荷的实时状况,当SV稳定而FTc<350 ms提示可能存在后负荷不足,通过去甲肾上腺素改变后负荷,维持循环的稳定,提高器官的灌注从而改善氧供和减少过多输液带来的不利影响。

    从本研究的结果中可以看出观察组术中的血流动力学指标、尿量、晶/胶体的输注量比例均符合多数GDFT相关研究得出的结论。GIRAMUDO等[12]研究气腹对肝功能的影响发现术后气腹病人的AST、ALT要明显高于无气腹病人,这可能与手术体位导致的肝脏血流变化所致。但在本研究中2组病人手术前后的改变不明显,2组之间比较差异无统计学意义。术后恶心呕吐、谵妄等麻醉相关不良反应的发生率2组间差异无统计学意义。并发症发生情况中,对照组的并发症发生率明显高于观察组,其中肺部感染尤为明显,这说明观察组的术中液体管理策略会改善预后,病人术后恢复具有优势。由于受到样本量的限制,这种策略最终能否使高危病人受益,还需要大样本随机对照研究。

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