极化液对围术期老年患者室性心律失常和心率变异性的影响
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摘要
世界卫生组织报告显示,我国人均寿命已近73岁,最近全国人口普查表明,我国65岁以上老年人口比例为6.96%。随着年龄增长,老年人心脏电生理学改变可导致各种类型的心律失常频繁发生。频发多源性室性早搏、室性早搏二联律或三联律、室性心动过速等可使血流动力学发生改变,轻者引起患者不适,严重者可导致心功能失代偿,加重心肌缺血促使病情恶化,是老年人致死的重要因素之一,应及早诊断,及时予以治疗。老年病人在进行急诊和大中型手术时,较中青年患者更易诱发和加重各种心脏危险事件(CRE),高达12.8%,是严重威胁老年患者围术期生命安全的主要因素。因此,如何在术前预测围术期心脏事件的发生,术中、术后采取相应的防治措施,确保他们顺利度过围术期是许多临床工作者所关注的问题。一些研究表明,围术期用β受体阻滞剂、α_2肾上腺素受体阻滞剂及他汀类降脂药物治疗可以预防围术期心脏缺血事件的发生及降低死亡率,其中Mangano等还提出,服用β受体阻滞剂治疗可以减少术后两年内心脏事件的发生。葡萄糖-胰岛素-钾盐(Glucose-insulin-potassium,GIK,又称极化液)是传统经典药物组合,主要通过代谢调理来保护缺血的心肌细胞和心肌功能。这个概念早在1962年由Sodi-pallares等首次提出,通过大量临床观察和研究,1970年Opie在理论上进行更深入阐述,认为GIK可促进心肌细胞糖酵解和减少血清中的游离脂肪酸,其理论基础包括:①提供缺血心肌更多能量,胰岛素促进心肌细胞摄取和利用葡萄糖,最终促进缺血心肌功能恢复;②胰岛素刺激心肌细胞Na~+-K~+-ATP酶,促进心肌细胞摄取K~+,从而稳定细胞膜的极化状态,减少心律失常的发生。然而,随着GIK临床资料回顾性分析以及近年来该领域大量基础和临床研究,认为GIK具有许多新的药理学特性,如抗炎、抗凋亡、促修复、减少低排血量综合征(LOS)及心律失常、改善微循环和升高心率变异性等心血管保护效应。此外,Ranasinghe等研究发现,GIK可通过增加β_1肾上腺素能受体(betal-adrenergic receptor,ADRB1)和钙泵(SERCA2a)mRNA的表达来改善冠状动脉旁路移植术患者的血流动力学,提升心排血指数。
心率变异性(heart rate variability,HRV)分析是近年发展起来的一项定量评价心脏自主神经系统功能的新方法,在心血管疾病中的应用和研究日益广泛。有研究认为HRV减低是心脏性猝死的独立预测指标,HRV减小对猝死的预测与致死性室性心律失常有关。室性心律失常(VA)和心肌缺血等诸多心脏病理变化过程多伴有HRV的改变。
在临床中较长时间输注GIK对心肌的保护作用都集中在心脏手术或心肌梗死方面的研究且争议很多,而术中短时间输注极化液对非心脏手术患者室性心律失常(VA)和HRV的影响尚无明确定论,本研究想在这方面做些探讨。
目的
探讨术中持续输注葡萄糖-胰岛素-钾盐(GIK,又称极化液)对老年患者术后2天室性心律失常(VA)和心率变异性(HRV)的影响,GIK是否有益于老年人安全度过围术期。
方法
1.病例选择和分组从2008年1月到2008年10月,经过广州军区广州总医院伦理委员会的批准,对50名入院准备行腹部胃肠道、腰椎内固定、下肢手术的患者进行术前评估并签署同意书,ASA分级为Ⅰ～Ⅱ级,年龄≥65岁。排除标准包括:术前心电图检查发现左或右束支传导阻滞、心房颤动或扑动、起搏心律、肢体导联低电压者:术前生化检查发现高钾血症、低血糖者;术前或术后接受胰岛素、β受体阻滞剂、地高辛或奎尼丁等治疗者;对本研究药物有过敏史者;分为对照组(C组)和极化液组(G组)。
2.麻醉方法麻醉前30min肌肉注射苯巴比妥钠2mg╱kg,硫酸阿托品0.01mg/kg。入手术室平静10min后监测心电图(ECG)、无创血压(BP)、脉搏血氧饱和度(SpO_2)。腹部或者腰椎手术采用气管插管全麻,氟芬合剂(氟哌利多与芬太尼按50:1混合)4.0ml,丙泊酚1.0～1.5mg/kg,顺式阿曲库铵0.2mg/kg,依次静脉注射诱导插管。术中麻醉机控制呼吸,潮气量8～10ml/kg,呼吸频率12～14次/分钟,P_(ET)CO_2控制在30～40mmHg,采用丙泊酚4～6mg·kg~(-1)·h~(-1)复合瑞芬太尼0.1～0.2μg·kg~(-1)·min~(-1)全凭静脉麻醉维持,根据需要静脉注射顺式阿曲库铵0.1mg/kg维持肌松;下肢手术采用腰硬联合麻醉,于L3/4或L4/5穿刺,蛛网膜下腔注入0.5%布比卡因7～12mg,然后置入硬膜外导管大约3.0～5.0cm,麻醉平面控制在T_(10)左右,术中硬膜外根据需要适当追加1%利多卡因+0.25%左旋布比卡因3.0～5.0ml。术中输注平衡液和胶体液维持血容量,G组检测完血糖后即输注GIK(50%GS50ml+正规胰岛素10IU+10%KCl3ml)0.4ml·kg~(-1)·h~(-1)至手术结束。用罗康全活力型血糖检测仪分别在麻醉前、手术开始、手术结束检测所有患者末梢血糖。血糖低于3.0mmol/L时静脉注射50%GS20～40ml。
3.术后镇痛全麻患者术后接受静脉自控镇痛(PCIA),药物配方:凯纷150mg+喷他佐辛90mg混合液用生理盐水稀释至100ml,负荷量:凯纷50mg+喷他佐辛30mg,1.5～2.0ml/h维持,PCA为1.5～2.0ml,锁定时间30min。腰硬联合麻醉患者术后接受硬膜外自控镇痛(PCEA),药物配方:0.125%左旋布比卡因+布托啡诺5mg混合液用生理盐水稀释至100ml,负荷量:布托啡诺1mg,1.5～2.0ml/h维持,PCA为1.5～2.0ml,锁定时间30min。术后PCA泵最初的维持速度和负荷量由专门的麻醉医生来调节,使患者在临床状况平稳的前提下能够耐受疼痛和保持平静。在术后6h、12h、24h、36h、48h由专门的麻醉医生按照标准视觉模拟评分法(VAS)对患者进行疼痛评分,0分表示无痛,1～3分表示轻痛,4～6分表示中度痛,7～9分表示重度痛,10分表示剧痛。如果VAS评分超过4分,那么PCA维持速度增加1/3,并给予一个3.0～5.0ml负荷量。如果疼痛仍然很剧烈,静脉注射喷他佐辛30mg。
4.动态心电图监测采用多通道动态心电图记录患者术前12h,术后48h心电图资料,并将其输入电脑由专门的软件(DMS Holter 5.0,USA)进行分析。由专门的技术人员对采集的数据进行分析,并对软件生成的报告进行监测核对。常见室性心律失常包括室性早搏、成对室性早搏、频发室性早搏、室性心动过速。HRV分析方法包括时域分析及频域分析。时域分析指标为:(1)正常R-R间期的标准差(SDNN);(2)每5min正常R-R间期标准差的平均值(SDNNindex);(3)每5min正常R-R间期平均值的标准差(SDANNindex);(4)相邻正常R-R间期差值的均方根(rMSSD);(5)相邻两正常R-R间期差值大于50ms的心搏数所占百分数(PNN50)。频域指标为总功率(TP:0.01～0.4 Hz)、高频功率(HF:0.15～0.4Hz)、低频功率(LF:0.04～0.15 HZ)、极低频功率(VLF:0.003～0.04 Hz)及LF/HF。
结果
从2008年1月到2008年10月,对50名入院预行腹部、腰椎内固定、下肢手术的患者进行术前评估和筛选,18名患者被排除(主要是因为手术后患者拒绝动态心电图监测或电极脱落或心电图形干扰太大无法分析或两组麻醉方法不均衡),最终32名患者进入本试验,分为对照组(C组,n=16)和极化液组(G组,n=16)。
1、两组患者一般资料的比较
两组性别、年龄、体重、手术部位、麻醉方法等没有显著差异;两组术中没有严重、持久的心率、血压及脉搏血氧饱和度异常。
2、两组患者术后VAS评分组间比较无显著差异
3、两组患者手术中各时间点血糖值的比较
C组三个时间点的血糖值逐渐升高,手术开始和结束时的血糖值较麻醉前有显著差异(P=0.000 and P=0.000),G组血糖值先升高后降低,手术开始时的血糖值较麻醉前有显著差异(P=0.024),但手术结束时的血糖值较麻醉前没有显著差异;两组间比较手术开始和手术结束有显著差异(F=10.964,P=0.002 and F=33.689,P=0.000)。
4、两组患者手术前后室性心律失常(VA)发生情况的比较
93.75%的患者经历了室性心律失常,没有出现室扑和室颤。G组室性早搏手术前后有显著差异(x~2=18.072,P=0.001),随着手术后时间的延长,室性早搏数显著减少(平均秩次从手术前到手术后48h各个时间段呈减小趋势,分别是:4.06 vs 3.53 vs 2.63vs 2.66 vs 2.13),C组手术前后没有显著差异;两组间比较:术后24h、36h、48h三个时间段中较前一个时间段室性早搏发生个数呈增加的患者数比较有显著差异(10/1 vs3/8,x~2=9.214,P=0.008 and 8/4 vs 2/8,x~2=4.791,P=0.043 and 10/1 vs 2/5,x~2=7.418,P=0.013),C组的患者数显著多于G组。两组间有效率比较:G组术后36h、48h两个时间段的室性早搏有效率显著高于C组(11/16 vs 4/16,x~2=6.149,P=0.032 and 10/16 vs2/16,x~2=8.533,P=0.009),G组术后24h、36h、48h两个时间段的室性心律失常有效率显著高于C组(12/16 vs 3/16,x~2=10.165,P=0.004 and 13/16 vs 4/16,x~2=10.165,P=0.004 and 12/16 vs 2/16,x~2=12.698,P=0.001);术后2天室性心律失常总有效率G组较C组高50%(13/64 vs 45/64,x~2=32.284,P=0.000)。
5、两组患者手术前后心率变异性(HRV)的比较
两组患者手术前后SDNN、SDANNindex、SDNNindex、rMSSD、TP、HF、LF和VLF有显著差异(P=0.000 and P=0.000 and P=0.000 and P=0.002 and P=0.000 andP=0.000 and P=0.000 and P=0.000),手术后显著低于手术前。手术后2天比较没有显著差异,但C组SDNN、SDANNindex、SDNNindex、rMSSD和TP逐渐降低,G组相应指标则呈回升趋势。手术后第2天两组间比较TP、VLF和SDNN有显著差异(F=5.497,P=0.026 and F=4.762,P=0.037 and F=4.216,P=0.049),G组显著高于C组。
结论
本研究通过术中对非心脏手术老年患者持续输注大剂量极化液,观察术中指尖血糖、术后2天室性心律失常和心率变异性的变化,得出如下结论:
极化液可以适当地控制手术期间的应激性高血糖,可能会减轻高血糖对机体的损害;可以使术后2天室性心律失常的发生减少50%,可能会使血流动力学波动较小;可以抑制术后2天心率变异性的显著降低,可能会减轻老年人手术后心脏自主神经系统受损害程度;总之,术中输注大剂量极化液可能有益于老年患者安全度过围术期。
World Health Organization(WHO) report showed the life span of our country has already approached 73 years old.National census indicated that the proportion of 65 years old person to our population is 8.51%rencently.With age increasing,the changes of cordis electricity physiology in the aged people could be frequently associated with various cardiacarrhythmia(CA).Frequent multi-sources ventricular ectopic beats(FVEB),coupled rhythm or trigeminy of ventricular ectopic beats(VEB) and ventricular tachycardia(VT) etc. may change haemodynamics.Some patients were unwell,even were caused cardiac function broken compensation and urged myocardial ischemia.Those CA could result in serious consequence.It was one of the important factors that the aged people was caused death.It was necessary to examine early and give treatment in time.Compared with the youth,the aged patient who was carried out emergency or big and medium-sized surgical operations, was much easy to induct and aggravate various cardiac risk event(CRE),being up to 12.8%.It was the main factor that threaten the aged life safety of perioperative period seriously.Therefore,many clinical workeres pay attention how to predict the preoperative risk factors of CRE and to adopt corresponding measures during operation and after operation,as to insure they smoothly passed through perioperative period.Some studies expressed thatβ-receptor blockers,alpha(2)-adrenergic agonists and statins could prevent perioperative period heart ischemia affairs from generating and reducing mortality. Among them,Mangano et al still considered that the treatment withβ-receptor blockers during hospitalization could reduce mortality and the incidence of cardiovascular complications for as long as two years after surgery.Glucose-insulin-potassium(GIK,or called polarized solution) was a traditional classic old medicine,which mainly nursed one's health through metabolic modulation to protect ischemic myocardial cell and myocardial functions.This concept was introduced first time by the Sodi-pallares et al in 1962. Through a great deal of clinic observation and studying,Opie further elaborated theoretically in 1970 and believed that GIK could promote myocardial cell glycolysis and reduce serum free fatty acids(FFA).Its rationale foundation included:①to provide ischemic myocardium more energies,to let insulin promote myocardial cell uptake and make use of glucose,to promote the function instauration of ischemic myocardium at last;②insulin stimulated myocardial cell Na~+-K~+-ATP enzyme,promoted myocardial cell uptake K~+,thus stabilized polarization state of cytolemma,reduced the occurrence of cardiac arrhythmia. However,alonged with the clinical data review analysis on GIK and a great deal of foundational clinic studies of that realm in recent years,it was suggested that GIK had many new pharmacological characteristic,such as anti-inflammatory,anti-Apoptosis,promoted repair,reduction of low output syndromes(LOS) and cardiac arrhythmia,improvement of microcirculation and raise of HRV(heart rate variability) et al.cardiovascular protection effectiveness.In addition,Ranasinghe et al discovered that GIK improved hemodynamic performance after coronary artery bypass grafting(CABG).The beneficial increased cardiac index(CI) of GIK therapy was associated with increased ADRB1 and SERCA2a mRNA expression.
HRV analysis was a new method of quantitative assessment on cordis automatic nervous system function in recent years.The application and study in cardiovascular disease was increasingly extensive.Many studies have enunciated that HRV abaissement was the independent estimate index of sudden cardiac death.This anticipation had some thing to do with fatal ventricular arrhythmia(VA).Many heart pathological change processes, especially VA and myocardial ischemia(MI) et al were often accompanied with changes of HRV.
These clinic studies that GIK infusion could protect myocardium at a long time were all concentrated on heart surgical operation or myocardial infarction,and existed a good deal of dispute.However,effects that GIK transient infusion on VA and HRV had no accepted argument.This study wants to do some approach in this aspect.
Objective To observe the influence of GIK application during the period of operation on VA and HRV of gerontal patient,we explored whether GIK was beneficial to the elderly people live through perioperative period steadily or not.
Methods
1.patients and groups
This study was approved by the institutional review board and informed written consent was obtained from each subject.Between January 2008 and October 2008,a total of 50 consecutive patients entered in the Guangzhou General Hospital of Guangzhou Military Command to force-progress stomach intestines,vertebra lumbalis internal fixation, extremitas inferior surgical operation were adopted preoperative evaluation,ASA gradeⅠorⅡ,age≥65 years old.Standard of depletion included:preoperative electrocardiogram check discovered that the left or right bundle branch conduction blockade,atrial fibrillation or atrial flutte,pacing cardiac rhythm,limb lead low tension;preoperative biochemistry check acquired hyperpotassaemia or hypoglycaemia;received insulin,β-receptor blocker,digoxin or conchine treatment perioperatively;hypersensitiveness history in investigative drug.All patients were divided into control group(group C) and GIK group(group G).
2.anaesthesia
Atropine 0.01mg/kg and phenobarbital sodium 2mg/kg were given i.m.approximately 30 minutes before anaesthisa.Electrocardiogram(ECG),noninvasive blood pressure,pulse blood oxygen saturation(SpO_2) were monitored after going into operating room and quieting 10 minutes.Abdomen or lumbar vertebrae operation was adopted endotracheal intubation anesthesia.Anaesthesia was induced i.v.one by one with innovar(droperidol and fentanyl were admixed by 50:1) 4ml,propofol 1.0～1.5mg/kg,benzenesulfonic acid cisatracurium 0.2mg/kg.Patients were ventilated by anaeshetic machine with tidal volume 8～10ml/kg, respiratory rate 12～14 breaths/min,and P_(ET)CO_2 was controlled at 30～40mmHg.Anaesthesia was maintained with propofol(4～6 mg·kg~(-1)·h~(-1)) and remifentanil(0.1～0.2μg·kg~(-1)·h~(-1)). Lower limbs operation was adopted combined spinal and epidural anaestesia(CSEA).An epidural transfixion pin was inserted at L3/4 or L4/5 interspace,cavitas subarachnoidealis was infused into 0.5%bupivcaine 7～12 mg,then epidural catheter was inserted into cavitas epiduralis approximately 3.0～5.0cm.Anaesthesia blockage plane was controlled about T_(10). The mixed liquor contained 1%lidocaine and 0.25%laevo-bupivcaine 3.0～5.0ml was reasonably infused into cavitas epiduralis according to demand.Balanced solution and colloid were dripped into maintaining blood volume.GIK therapy(50%dextrose 50ml, regular insulin 10 IU,and potassium chloride 4mmol) at a dose of 0.4 ml·kg~(-1)·h~(-1) was administered from anesthesia beginning until operation ending after measuring blood glucose.All patients were detected peripheral blood glucose by ACCU-CHEK Active respectively before anaesthesia,surgical operation beginning and ending.50%dextrose 20～40ml was given through intravenous injection when blood glucose level≤3.0mmol/L.
3.postoperative analgesia
During postoperative forty-eight hours,every patient received patient-controlled analgesia(PCA) through either the i.v.route(general anaesthesia patients) or epidural route (CSEA patients).Admixture of flurbiprofen axeyil 1.5 mg/ml and pentazocine 0.9 mg/ml was contained in PCIA pump.Laevo-bupivcaine 0.125%with butorphanol 0.05 mg/ml was contained in PCEA pump.All parameters of PCA pump were 1.5～2.0ml/h,PCA is 1.5～2.0 ml,caging time is 30 minutes.After surgery,the initial rate and bolus volume of PCA pump were adjusted by the special anaesthetist according to clinical situation to make patient calm.Pain scores were recorded at 6h,12h,24h,36h,48h after surgery.Recording of pain scores and parameters adjustment of PCA were performed by one of the authors blind to the group allocation.A standard visual analogue(VAS) for pain,0 score,1～3 score,4～6 score,7～9 score,10 score means no pain,mild pain,moderate pain,severe pain,agonia respectively.If the VAS score was more than 4,the PCA pump speed was increased by one third and a bonus of 3.0～5.0 ml was given.If the score remains high,i.v.pentazocine 30 mg was given.
4.ECG analysis
Multi-channel dynamic electrocardiographic(DCG) data of preoperative 12h and postoperative 48h,all patients were acquired and transfered for computerized analysis by software(DMS Holter 5.0 program,USA).The decisions made automatically by the computer were reviewed and reported by an experienced technician blind to group allocating. Frequent ventricular arrhythmias consist of ventricular ectopic beats,ventricular couplets, frequent ventricular ectopic beats,ventriculartachycardia.The analytical method of HRV included time domain analysis and frequency domain analysis.Time domain index contained(1) SDNN);(2) SDNNindex;(3)SDANNindex;(4)rMSSD;(5)PNN50.Frequency domain index contained total power(TP:0.01～0.4Hz),high frequency power(HF:0.15～0.4 Hz),low frequency power(LF:0.04～0.15Hz),very low frequency power(VLF:0.003～0.04 Hz) and LF/HF.
Results
1.Comparison of general numerical data between two groups.
There were no significant differences of sex,age,operative site,anaesthesia method etc. between two groups.
2.There was no significant difference of VAS scores between two groups.
3.Changes of blood glucose each moment between two groups during operation(P= 0.000 and P=0.000) were significant differences.The blood glucose levels of three times were on the increased in Control group,blood glucose levels of operation started and operation finished were much higher than that of before anesthesia(P=0.024).In GIK group,the blood glucose level steped up first,then cut down,but the blood glucose level of operation finished was no obviously slower than that of operation beginning.The blood glucose level between two groups was significant differences(F=6.360,P=0.017).
4.Comparison of perioperatively ventricular arrhythmias(VA) occurrence between two groups.
VA was almost appeared in overall patients perioperatively(93.75%,excepted for two patients),ventricular flutter and ventricular fibrillation did not appear.There was significant difference of VEB in GIK group(χ~2=18.072,P=0.001),their mean Rank was 4.06 vs 3.53 vs 2.63 vs 2.66 vs 2.13,but no significant difference in Control group perioperatively.There were significant difference of patient number that VEB appeared and its frequency increase at postoperative 24h,36h,48h between two groups(10/1 vs 3/8,χ~2=9.214,P=0.008 and 8/4 vs 2/8,χ~2=4.791,P=0.043 and 10/1 vs 2/5,χ~2=7.418,P=0.013),those of Control group was more than those of GIK group.
5.Comparison of HRV perioperatively between two groups.
There were significant differences of SDNN,SDANNindex,SDNNindex,rMSSD,TP, HF,LF and VLF perioperatively between two group(P=0.000 and P=0.000 and P=0.000 and P=0.002 and P=0.000 and P=0.000 and P=0.000 and P=0.000),those of before operation were lower than those of after operation.SDNN,SDANNindex,SDNNindex,rMSSD and TP were no significant differences between the first day and the second day after operation. They cut down gradually in Control group,but opposite in GIK group.There was significant difference of SDNN between two groups(F=4.518,P=0.042).That of GIK group was much higher than control group.
Conclusion
Application of this component GIK could control stress hyperglycemia properly,decrease the occurrence of VA(ventricular arrhythmias) in two days after operation and prevent HRV from going down in two days after operation.It was beneficial to the elderly people live through perioperative period safely.
心率变异性(heart rate variability,HRV)分析是近年发展起来的一项定量评价心脏自主神经系统功能的新方法,在心血管疾病中的应用和研究日益广泛。有研究认为HRV减低是心脏性猝死的独立预测指标,HRV减小对猝死的预测与致死性室性心律失常有关。室性心律失常(VA)和心肌缺血等诸多心脏病理变化过程多伴有HRV的改变。
在临床中较长时间输注GIK对心肌的保护作用都集中在心脏手术或心肌梗死方面的研究且争议很多,而术中短时间输注极化液对非心脏手术患者室性心律失常(VA)和HRV的影响尚无明确定论,本研究想在这方面做些探讨。
目的
探讨术中持续输注葡萄糖-胰岛素-钾盐(GIK,又称极化液)对老年患者术后2天室性心律失常(VA)和心率变异性(HRV)的影响,GIK是否有益于老年人安全度过围术期。
方法
1.病例选择和分组从2008年1月到2008年10月,经过广州军区广州总医院伦理委员会的批准,对50名入院准备行腹部胃肠道、腰椎内固定、下肢手术的患者进行术前评估并签署同意书,ASA分级为Ⅰ～Ⅱ级,年龄≥65岁。排除标准包括:术前心电图检查发现左或右束支传导阻滞、心房颤动或扑动、起搏心律、肢体导联低电压者:术前生化检查发现高钾血症、低血糖者;术前或术后接受胰岛素、β受体阻滞剂、地高辛或奎尼丁等治疗者;对本研究药物有过敏史者;分为对照组(C组)和极化液组(G组)。
2.麻醉方法麻醉前30min肌肉注射苯巴比妥钠2mg╱kg,硫酸阿托品0.01mg/kg。入手术室平静10min后监测心电图(ECG)、无创血压(BP)、脉搏血氧饱和度(SpO_2)。腹部或者腰椎手术采用气管插管全麻,氟芬合剂(氟哌利多与芬太尼按50:1混合)4.0ml,丙泊酚1.0～1.5mg/kg,顺式阿曲库铵0.2mg/kg,依次静脉注射诱导插管。术中麻醉机控制呼吸,潮气量8～10ml/kg,呼吸频率12～14次/分钟,P_(ET)CO_2控制在30～40mmHg,采用丙泊酚4～6mg·kg~(-1)·h~(-1)复合瑞芬太尼0.1～0.2μg·kg~(-1)·min~(-1)全凭静脉麻醉维持,根据需要静脉注射顺式阿曲库铵0.1mg/kg维持肌松;下肢手术采用腰硬联合麻醉,于L3/4或L4/5穿刺,蛛网膜下腔注入0.5%布比卡因7～12mg,然后置入硬膜外导管大约3.0～5.0cm,麻醉平面控制在T_(10)左右,术中硬膜外根据需要适当追加1%利多卡因+0.25%左旋布比卡因3.0～5.0ml。术中输注平衡液和胶体液维持血容量,G组检测完血糖后即输注GIK(50%GS50ml+正规胰岛素10IU+10%KCl3ml)0.4ml·kg~(-1)·h~(-1)至手术结束。用罗康全活力型血糖检测仪分别在麻醉前、手术开始、手术结束检测所有患者末梢血糖。血糖低于3.0mmol/L时静脉注射50%GS20～40ml。
3.术后镇痛全麻患者术后接受静脉自控镇痛(PCIA),药物配方:凯纷150mg+喷他佐辛90mg混合液用生理盐水稀释至100ml,负荷量:凯纷50mg+喷他佐辛30mg,1.5～2.0ml/h维持,PCA为1.5～2.0ml,锁定时间30min。腰硬联合麻醉患者术后接受硬膜外自控镇痛(PCEA),药物配方:0.125%左旋布比卡因+布托啡诺5mg混合液用生理盐水稀释至100ml,负荷量:布托啡诺1mg,1.5～2.0ml/h维持,PCA为1.5～2.0ml,锁定时间30min。术后PCA泵最初的维持速度和负荷量由专门的麻醉医生来调节,使患者在临床状况平稳的前提下能够耐受疼痛和保持平静。在术后6h、12h、24h、36h、48h由专门的麻醉医生按照标准视觉模拟评分法(VAS)对患者进行疼痛评分,0分表示无痛,1～3分表示轻痛,4～6分表示中度痛,7～9分表示重度痛,10分表示剧痛。如果VAS评分超过4分,那么PCA维持速度增加1/3,并给予一个3.0～5.0ml负荷量。如果疼痛仍然很剧烈,静脉注射喷他佐辛30mg。
4.动态心电图监测采用多通道动态心电图记录患者术前12h,术后48h心电图资料,并将其输入电脑由专门的软件(DMS Holter 5.0,USA)进行分析。由专门的技术人员对采集的数据进行分析,并对软件生成的报告进行监测核对。常见室性心律失常包括室性早搏、成对室性早搏、频发室性早搏、室性心动过速。HRV分析方法包括时域分析及频域分析。时域分析指标为:(1)正常R-R间期的标准差(SDNN);(2)每5min正常R-R间期标准差的平均值(SDNNindex);(3)每5min正常R-R间期平均值的标准差(SDANNindex);(4)相邻正常R-R间期差值的均方根(rMSSD);(5)相邻两正常R-R间期差值大于50ms的心搏数所占百分数(PNN50)。频域指标为总功率(TP:0.01～0.4 Hz)、高频功率(HF:0.15～0.4Hz)、低频功率(LF:0.04～0.15 HZ)、极低频功率(VLF:0.003～0.04 Hz)及LF/HF。
结果
从2008年1月到2008年10月,对50名入院预行腹部、腰椎内固定、下肢手术的患者进行术前评估和筛选,18名患者被排除(主要是因为手术后患者拒绝动态心电图监测或电极脱落或心电图形干扰太大无法分析或两组麻醉方法不均衡),最终32名患者进入本试验,分为对照组(C组,n=16)和极化液组(G组,n=16)。
1、两组患者一般资料的比较
两组性别、年龄、体重、手术部位、麻醉方法等没有显著差异;两组术中没有严重、持久的心率、血压及脉搏血氧饱和度异常。
2、两组患者术后VAS评分组间比较无显著差异
3、两组患者手术中各时间点血糖值的比较
C组三个时间点的血糖值逐渐升高,手术开始和结束时的血糖值较麻醉前有显著差异(P=0.000 and P=0.000),G组血糖值先升高后降低,手术开始时的血糖值较麻醉前有显著差异(P=0.024),但手术结束时的血糖值较麻醉前没有显著差异;两组间比较手术开始和手术结束有显著差异(F=10.964,P=0.002 and F=33.689,P=0.000)。
4、两组患者手术前后室性心律失常(VA)发生情况的比较
93.75%的患者经历了室性心律失常,没有出现室扑和室颤。G组室性早搏手术前后有显著差异(x~2=18.072,P=0.001),随着手术后时间的延长,室性早搏数显著减少(平均秩次从手术前到手术后48h各个时间段呈减小趋势,分别是:4.06 vs 3.53 vs 2.63vs 2.66 vs 2.13),C组手术前后没有显著差异;两组间比较:术后24h、36h、48h三个时间段中较前一个时间段室性早搏发生个数呈增加的患者数比较有显著差异(10/1 vs3/8,x~2=9.214,P=0.008 and 8/4 vs 2/8,x~2=4.791,P=0.043 and 10/1 vs 2/5,x~2=7.418,P=0.013),C组的患者数显著多于G组。两组间有效率比较:G组术后36h、48h两个时间段的室性早搏有效率显著高于C组(11/16 vs 4/16,x~2=6.149,P=0.032 and 10/16 vs2/16,x~2=8.533,P=0.009),G组术后24h、36h、48h两个时间段的室性心律失常有效率显著高于C组(12/16 vs 3/16,x~2=10.165,P=0.004 and 13/16 vs 4/16,x~2=10.165,P=0.004 and 12/16 vs 2/16,x~2=12.698,P=0.001);术后2天室性心律失常总有效率G组较C组高50%(13/64 vs 45/64,x~2=32.284,P=0.000)。
5、两组患者手术前后心率变异性(HRV)的比较
两组患者手术前后SDNN、SDANNindex、SDNNindex、rMSSD、TP、HF、LF和VLF有显著差异(P=0.000 and P=0.000 and P=0.000 and P=0.002 and P=0.000 andP=0.000 and P=0.000 and P=0.000),手术后显著低于手术前。手术后2天比较没有显著差异,但C组SDNN、SDANNindex、SDNNindex、rMSSD和TP逐渐降低,G组相应指标则呈回升趋势。手术后第2天两组间比较TP、VLF和SDNN有显著差异(F=5.497,P=0.026 and F=4.762,P=0.037 and F=4.216,P=0.049),G组显著高于C组。
结论
本研究通过术中对非心脏手术老年患者持续输注大剂量极化液,观察术中指尖血糖、术后2天室性心律失常和心率变异性的变化,得出如下结论:
极化液可以适当地控制手术期间的应激性高血糖,可能会减轻高血糖对机体的损害;可以使术后2天室性心律失常的发生减少50%,可能会使血流动力学波动较小;可以抑制术后2天心率变异性的显著降低,可能会减轻老年人手术后心脏自主神经系统受损害程度;总之,术中输注大剂量极化液可能有益于老年患者安全度过围术期。
World Health Organization(WHO) report showed the life span of our country has already approached 73 years old.National census indicated that the proportion of 65 years old person to our population is 8.51%rencently.With age increasing,the changes of cordis electricity physiology in the aged people could be frequently associated with various cardiacarrhythmia(CA).Frequent multi-sources ventricular ectopic beats(FVEB),coupled rhythm or trigeminy of ventricular ectopic beats(VEB) and ventricular tachycardia(VT) etc. may change haemodynamics.Some patients were unwell,even were caused cardiac function broken compensation and urged myocardial ischemia.Those CA could result in serious consequence.It was one of the important factors that the aged people was caused death.It was necessary to examine early and give treatment in time.Compared with the youth,the aged patient who was carried out emergency or big and medium-sized surgical operations, was much easy to induct and aggravate various cardiac risk event(CRE),being up to 12.8%.It was the main factor that threaten the aged life safety of perioperative period seriously.Therefore,many clinical workeres pay attention how to predict the preoperative risk factors of CRE and to adopt corresponding measures during operation and after operation,as to insure they smoothly passed through perioperative period.Some studies expressed thatβ-receptor blockers,alpha(2)-adrenergic agonists and statins could prevent perioperative period heart ischemia affairs from generating and reducing mortality. Among them,Mangano et al still considered that the treatment withβ-receptor blockers during hospitalization could reduce mortality and the incidence of cardiovascular complications for as long as two years after surgery.Glucose-insulin-potassium(GIK,or called polarized solution) was a traditional classic old medicine,which mainly nursed one's health through metabolic modulation to protect ischemic myocardial cell and myocardial functions.This concept was introduced first time by the Sodi-pallares et al in 1962. Through a great deal of clinic observation and studying,Opie further elaborated theoretically in 1970 and believed that GIK could promote myocardial cell glycolysis and reduce serum free fatty acids(FFA).Its rationale foundation included:①to provide ischemic myocardium more energies,to let insulin promote myocardial cell uptake and make use of glucose,to promote the function instauration of ischemic myocardium at last;②insulin stimulated myocardial cell Na~+-K~+-ATP enzyme,promoted myocardial cell uptake K~+,thus stabilized polarization state of cytolemma,reduced the occurrence of cardiac arrhythmia. However,alonged with the clinical data review analysis on GIK and a great deal of foundational clinic studies of that realm in recent years,it was suggested that GIK had many new pharmacological characteristic,such as anti-inflammatory,anti-Apoptosis,promoted repair,reduction of low output syndromes(LOS) and cardiac arrhythmia,improvement of microcirculation and raise of HRV(heart rate variability) et al.cardiovascular protection effectiveness.In addition,Ranasinghe et al discovered that GIK improved hemodynamic performance after coronary artery bypass grafting(CABG).The beneficial increased cardiac index(CI) of GIK therapy was associated with increased ADRB1 and SERCA2a mRNA expression.
HRV analysis was a new method of quantitative assessment on cordis automatic nervous system function in recent years.The application and study in cardiovascular disease was increasingly extensive.Many studies have enunciated that HRV abaissement was the independent estimate index of sudden cardiac death.This anticipation had some thing to do with fatal ventricular arrhythmia(VA).Many heart pathological change processes, especially VA and myocardial ischemia(MI) et al were often accompanied with changes of HRV.
These clinic studies that GIK infusion could protect myocardium at a long time were all concentrated on heart surgical operation or myocardial infarction,and existed a good deal of dispute.However,effects that GIK transient infusion on VA and HRV had no accepted argument.This study wants to do some approach in this aspect.
Objective To observe the influence of GIK application during the period of operation on VA and HRV of gerontal patient,we explored whether GIK was beneficial to the elderly people live through perioperative period steadily or not.
Methods
1.patients and groups
This study was approved by the institutional review board and informed written consent was obtained from each subject.Between January 2008 and October 2008,a total of 50 consecutive patients entered in the Guangzhou General Hospital of Guangzhou Military Command to force-progress stomach intestines,vertebra lumbalis internal fixation, extremitas inferior surgical operation were adopted preoperative evaluation,ASA gradeⅠorⅡ,age≥65 years old.Standard of depletion included:preoperative electrocardiogram check discovered that the left or right bundle branch conduction blockade,atrial fibrillation or atrial flutte,pacing cardiac rhythm,limb lead low tension;preoperative biochemistry check acquired hyperpotassaemia or hypoglycaemia;received insulin,β-receptor blocker,digoxin or conchine treatment perioperatively;hypersensitiveness history in investigative drug.All patients were divided into control group(group C) and GIK group(group G).
2.anaesthesia
Atropine 0.01mg/kg and phenobarbital sodium 2mg/kg were given i.m.approximately 30 minutes before anaesthisa.Electrocardiogram(ECG),noninvasive blood pressure,pulse blood oxygen saturation(SpO_2) were monitored after going into operating room and quieting 10 minutes.Abdomen or lumbar vertebrae operation was adopted endotracheal intubation anesthesia.Anaesthesia was induced i.v.one by one with innovar(droperidol and fentanyl were admixed by 50:1) 4ml,propofol 1.0～1.5mg/kg,benzenesulfonic acid cisatracurium 0.2mg/kg.Patients were ventilated by anaeshetic machine with tidal volume 8～10ml/kg, respiratory rate 12～14 breaths/min,and P_(ET)CO_2 was controlled at 30～40mmHg.Anaesthesia was maintained with propofol(4～6 mg·kg~(-1)·h~(-1)) and remifentanil(0.1～0.2μg·kg~(-1)·h~(-1)). Lower limbs operation was adopted combined spinal and epidural anaestesia(CSEA).An epidural transfixion pin was inserted at L3/4 or L4/5 interspace,cavitas subarachnoidealis was infused into 0.5%bupivcaine 7～12 mg,then epidural catheter was inserted into cavitas epiduralis approximately 3.0～5.0cm.Anaesthesia blockage plane was controlled about T_(10). The mixed liquor contained 1%lidocaine and 0.25%laevo-bupivcaine 3.0～5.0ml was reasonably infused into cavitas epiduralis according to demand.Balanced solution and colloid were dripped into maintaining blood volume.GIK therapy(50%dextrose 50ml, regular insulin 10 IU,and potassium chloride 4mmol) at a dose of 0.4 ml·kg~(-1)·h~(-1) was administered from anesthesia beginning until operation ending after measuring blood glucose.All patients were detected peripheral blood glucose by ACCU-CHEK Active respectively before anaesthesia,surgical operation beginning and ending.50%dextrose 20～40ml was given through intravenous injection when blood glucose level≤3.0mmol/L.
3.postoperative analgesia
During postoperative forty-eight hours,every patient received patient-controlled analgesia(PCA) through either the i.v.route(general anaesthesia patients) or epidural route (CSEA patients).Admixture of flurbiprofen axeyil 1.5 mg/ml and pentazocine 0.9 mg/ml was contained in PCIA pump.Laevo-bupivcaine 0.125%with butorphanol 0.05 mg/ml was contained in PCEA pump.All parameters of PCA pump were 1.5～2.0ml/h,PCA is 1.5～2.0 ml,caging time is 30 minutes.After surgery,the initial rate and bolus volume of PCA pump were adjusted by the special anaesthetist according to clinical situation to make patient calm.Pain scores were recorded at 6h,12h,24h,36h,48h after surgery.Recording of pain scores and parameters adjustment of PCA were performed by one of the authors blind to the group allocation.A standard visual analogue(VAS) for pain,0 score,1～3 score,4～6 score,7～9 score,10 score means no pain,mild pain,moderate pain,severe pain,agonia respectively.If the VAS score was more than 4,the PCA pump speed was increased by one third and a bonus of 3.0～5.0 ml was given.If the score remains high,i.v.pentazocine 30 mg was given.
4.ECG analysis
Multi-channel dynamic electrocardiographic(DCG) data of preoperative 12h and postoperative 48h,all patients were acquired and transfered for computerized analysis by software(DMS Holter 5.0 program,USA).The decisions made automatically by the computer were reviewed and reported by an experienced technician blind to group allocating. Frequent ventricular arrhythmias consist of ventricular ectopic beats,ventricular couplets, frequent ventricular ectopic beats,ventriculartachycardia.The analytical method of HRV included time domain analysis and frequency domain analysis.Time domain index contained(1) SDNN);(2) SDNNindex;(3)SDANNindex;(4)rMSSD;(5)PNN50.Frequency domain index contained total power(TP:0.01～0.4Hz),high frequency power(HF:0.15～0.4 Hz),low frequency power(LF:0.04～0.15Hz),very low frequency power(VLF:0.003～0.04 Hz) and LF/HF.
Results
1.Comparison of general numerical data between two groups.
There were no significant differences of sex,age,operative site,anaesthesia method etc. between two groups.
2.There was no significant difference of VAS scores between two groups.
3.Changes of blood glucose each moment between two groups during operation(P= 0.000 and P=0.000) were significant differences.The blood glucose levels of three times were on the increased in Control group,blood glucose levels of operation started and operation finished were much higher than that of before anesthesia(P=0.024).In GIK group,the blood glucose level steped up first,then cut down,but the blood glucose level of operation finished was no obviously slower than that of operation beginning.The blood glucose level between two groups was significant differences(F=6.360,P=0.017).
4.Comparison of perioperatively ventricular arrhythmias(VA) occurrence between two groups.
VA was almost appeared in overall patients perioperatively(93.75%,excepted for two patients),ventricular flutter and ventricular fibrillation did not appear.There was significant difference of VEB in GIK group(χ~2=18.072,P=0.001),their mean Rank was 4.06 vs 3.53 vs 2.63 vs 2.66 vs 2.13,but no significant difference in Control group perioperatively.There were significant difference of patient number that VEB appeared and its frequency increase at postoperative 24h,36h,48h between two groups(10/1 vs 3/8,χ~2=9.214,P=0.008 and 8/4 vs 2/8,χ~2=4.791,P=0.043 and 10/1 vs 2/5,χ~2=7.418,P=0.013),those of Control group was more than those of GIK group.
5.Comparison of HRV perioperatively between two groups.
There were significant differences of SDNN,SDANNindex,SDNNindex,rMSSD,TP, HF,LF and VLF perioperatively between two group(P=0.000 and P=0.000 and P=0.000 and P=0.002 and P=0.000 and P=0.000 and P=0.000 and P=0.000),those of before operation were lower than those of after operation.SDNN,SDANNindex,SDNNindex,rMSSD and TP were no significant differences between the first day and the second day after operation. They cut down gradually in Control group,but opposite in GIK group.There was significant difference of SDNN between two groups(F=4.518,P=0.042).That of GIK group was much higher than control group.
Conclusion
Application of this component GIK could control stress hyperglycemia properly,decrease the occurrence of VA(ventricular arrhythmias) in two days after operation and prevent HRV from going down in two days after operation.It was beneficial to the elderly people live through perioperative period safely.
引文
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[3]Butterworth J,Furberg CD.Improving cardiac outcomes after noncardiac surgery[J].Anesth Analg,2003,97(3):613-615.
[4]Wijeysundera DN,Naik JS,Beattie WS.Alpha-2 adrenergic agonists to prevent perioperative cardiovascular complications:a meta-analysis[J].Am J Med,2003,114(9):742-752.
[5]SODI-PALLARES D,TESTELLI MR,FISHLEDER BL,et al.Effects of an intravenous infusion of a potassium-glucose-insulin solution on the electrocardiographic signs of myocardial infarction.A preliminary clinical report[J].Am J Cardiol,1962,9:166-181.
[6]Opie LH.The glucose hypothesis:relation to acute myocardial ischaemia[J].J Mol Cell Cardiol,1970,1:107-114.
[7]Kloner RA,Nesto RW.Glucose-insulin-potassium for acute myocardial infarction:continuing controversy over cardioprotection[J].Circulation,2008,117(19):2523-2533.
[8]Luna Ortiz P,Serrano Valdes X,Rojas Perez E,et al.[Metabolic support of the ischemic heart during cardiac surgery][J].Arch Cardiol Mex,2006,76 Suppl 4:S 121-136.
[9]Turel B,Gemici K,Baran I,et al.Effects of glucose-insulin-potassium solution added to reperfusion treatment in acute myocardial infarction[J].Anadolu Kardiyol Derg,2005,5(2):90-94.
[10]Ranasinghe AM,McCabe CJ,Quinn DW,et al.How does glucose insulin potassium improve hemodynamic performance? Evidence for altered expression of beta-adrenoreceptor and calcium handling genes[J].Circulation,2006,114(1 Suppl):I239-244.
[11]Tsuji H,Venditti FJ Jr,Manders ES,et al.Reduced heart rate variability and mortality risk in an elderly cohort.The Framingham Heart Study[J].Circulation,1994,90(2):878-883.
[12]Algra A,Tijssen JG,Roelandt JR,et al.Heart rate variability from 24-hour electrocardiography and the 2-year risk for sudden death[J].Circulation,1993,88(1):180-185.
[13]唐继志,方永生,孙华群,等.室性心律失常患者的心率变异性分析[J].心电学杂志,2000,19(3):134-136.
[14]戴建强,屠伟峰,张军龙,等.围术期室性心律失常与心率变异性相关性的临床研究[J].实用医学杂志,2005,21(24):2725-2726.
[15]Poldermans D,Boersma E,Bax JJ,et al.The effect of bisoprolol on perioperative mortality and myocardial infarction in high-risk patients undergoing vascular surgery.Dutch Echocardiographic Cardiac Risk Evaluation Applying Stress Echocardiography Study Group[J].N Engl J Med,1999,341(24):1789-1794.
[16]Shim YH,Kweon TD,Lee JH,et al.Intravenous glucose-insulin-potassium during off-pump coronary artery bypass surgery does not reduce myocardial injury[J].Acta Anaesthesiol Scand,2006,50(8):954-961.
[17]Lazar HL,Chipkin SR,Fitzgerald CA,et al.Tight glycemic control in diabetic coronary artery bypass graft patients improves perioperative outcomes and decreases recurrent ischemic events[J].Circulation,2004,109(12):1497-1502.
[18]施群力,吴端源,吴顺荣.强化极化液治疗心律失常╱心力衰竭121例临床观察[J]宁夏医学杂志,2000,22(12):724～726.
[19]Verma S,Maitland A,Weisel RD,et al.Hyperglycemia exaggerates ischemia reperfusion induced cardiomyocyte injury:reversal with endothelin antagonism[J].J Thorac Cardiovasc Surg,2002,123(6):1120-1124.
[20]Zarich SW.Mechanism by which hyperglycemia plays a role in the setting of acute cardiovascular illness[J].Rev Cardiovasc Med,2006,7 Suppl 2:S35-43.
[21]Umpierrez GE,Isaacs SD,Bazargan N,et al.Hyperglycemia:an independent marker of in-hospital mortality in patients with undiagnosed diabetes[J].J Clin Endocrinol Metab,2002,87(3):978-982.
[22]Robinson LE,van Soeren MH.Insulin resistance and hyperglycemia in critical illness:role of insulin in glycemic control[J].AACN Clin Issues,2004,15(1):45-62.
[23]Lewis KS,Kane-Gill SL,Bobek MB,et al.Intensive insulin therapy for critically ill patients[J].Ann Pharmacother,2004,38(7-8):1243-1251.
[24]柴长春,王占科,胡新勇,邓宏,汪仕良,李光伟.严重创伤患者胰岛β细胞功能不全与极化液临床干预效果研究[J].江西医学院学报,2005,45(5):46-49.
[25]Diaz R,Paolasso EA,Piegas LS,et al.Metabolic modulation of acute myocardial infarction.The ECLA(Estudios Cardiologicos Latinoamerica) Collaborative Group[J].Circulation,1998,98(21):2227-2234.
[26]Zuurbier CJ,Hoek FJ,van Dijk J,et al.Perioperative hyperinsulinaemic normoglycaemic clamp causes hypolipidaemia after coronary artery surgery[J].Br J Anaesth,2008,100(4):442-450.
[27]Doenst T,Richwine RT,Bray MS,et al.Insulin improves functional and metabolic recovery of reperfused working rat heart[J].Ann Thorac Surg,1999,67(6):1682-1688.
[28]Heart rate variability:standards of measurement,physiological interpretation and clinical use.Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology[J].Circulation,1996,93(5):1043-1065.
[29]全国心率变异性分析多中心研究协作组.心率变异性正常值及其重复性的多中心研究[J].中华心律失常杂志,2000,4(3):165-170.
[30]陆再英.心率变异分析方法学的标准化及结果的正确评价[J].中国心脏起搏与心电生理杂志,1996,10(4):222-224.
[31]Schwartz PJ,La Rovere MT,Vanoli E.Autonomic nervous system and sudden cardiac death.Experimental basis and clinical observations for post-myocardial infarction risk stratification[J].Circulation,1992,85(1 Suppl):I77-91.
[32]Kleiger RE,Miller JP,Bigger JT Jr,et al.Decreased heart rate variability and its association with increased mortality after acute myocardial infarction[J].Am J Cardiol,1987,59(4):256-262.
[33]Rich MW,Saini JS,Kleiger RE,et al.Correlation of heart rate variability with clinical and angiographic variables and late mortality after coronary angiography[J].Am J Cardiol,1988,62(10 Pt 1):714-717.
[34]李上共,黄元伟,朱建华,等.室性心律失常与心率变异性的相关性研究[J].心功能杂志,1999,11(1):15-17.
[35]戴建强,屠伟峰.围术期成对室早或短阵室速发生前心率变异性的动态变化[J].临床麻醉学杂志,2002,18(7):351-353.
[36]Persson PB,Wagner CD.General principles of chaotic dynamics[J].Cardiovasc Res,1996,31(3):332-341.
[37]Farrell TG,Bashir Y,Cripps T,et al.Risk stratification for arrhythmic events in postinfarction patients based on heart rate variability,ambulatory electrocardiographic variables and the signal-averaged electrocardiogram[J].J Am Coll Cardiol,1991,18(3):687-697.
[38]Bigger JT Jr,Fleiss JL,Steinman RC,et al.Frequency domain measures of heart period variability and mortality after myocardial infarction[J].Circulation,1992,85(1):164-171.
[39]Huikuri HV,Valkama JO,Airaksinen KE,et al.Frequency domain measures of heart rate variability before the onset of nonsustained and sustained ventricular tachycardia in patients with coronary artery disease[J].Circulation,1993,87(4):1220-1228.
[40]Valkama JO,Huikuri HV,Koistinen MJ,et al.Relation between heart rate variability and spontaneous and induced ventricular arrhythmias in patients with coronary artery disease[J].J Am Coll Cardiol,1995,25(2):437-443.
[1]高峰,闫文莉,张海锋,等.胰岛素抑制缺血-再灌大鼠心肌细胞凋亡及其信号转导机制[J].中华内科杂志,2003,42(03):153-156.
[2]Jonassen AK,Aasum E,Riemersma RA,et al.Glucose-insulin-potassium reduces infarct size when administered during reperfusion[J].Cardiovasc Drugs Ther,2000,14(6):615-623.
[3]Zhang HF,Fan Q,Qian xx,et al.Role of insulin in the anti-apoptotic effect of glucose-insulin-potassium in rabbits with acute myocardial ischemia and reperfusion[J].Apoptosis,2004,9(6):777-783.
[4]Zhao ZQ,Morris CD,Budde JM,et al.Inhibition of myocardial apoptosis reduces infarct size and improves regional contractile dysfunction during reperfusion[J].Cardiovasc Res,2003,59(1):132-142.
[5]Jonassen AK,Sack MN,Mjos OD,et al.Myocardial protection by insulin at reperfusion requires early administration and is mediated via Akt and p70s6 kinase cell-survival signaling[J].Circ Res,2001,89(12):1191-1198.
[6]Gao F, Gao E, Yue TL, et al.Nitric oxide mediates the antiapoptotic effect of insulin in myocardial ischemia-reperfusion: the roles of PI3-kinase, Akt, and endothelial nitric oxide synthase phosphorylation[J].Circulation, 2002,105(12): 1497-1502.
[7]Federici M, Menghini R, Mauriello A, et al.Insulin-dependent activation of endothelial nitric oxide synthase is impaired by O-linked glycosylation modification of signaling proteins in human coronary endothelial cells[J].Circulation, 2002,106(4):466-472.
[8]Das UN.Is insulin an antiinflammatory molecule?[J].Nutrition, 2001,17(5):409-413.
[9]Dandona P, Aljada A, Bandyopadhyay A.Inflammation: the link between insulin resistance, obesity and diabetes[J].Trends Immunol, 2004,25(1):4-7.
[10]Malmberg K.Prospective randomised study of intensive insulin treatment on long term survival after acute myocardial infarction in patients with diabetes mellitus[J].DIGAMI (Diabetes Mellitus,Insulin Glucose Infusion in Acute Myocardial Infarction) Study Group.BMJ, 1997,314(7093): 1512-1515.
[11]Fath-Ordoubadi F, Beatt KJ.Glucose-insulin-potassium therapy for treatment of acute myocardial infarction: an overview of randomized placebo-controlled trials[J].Circulation,1997,96(4): 1152-1156.
[12]Diaz R, Paolasso EA, Piegas LS, et al.Metabolic modulation of acute myocardial infarction.The ECLA (Estudios Cardiologicos Latinoamerica) Collaborative Group.Circulation,1998,98(21):2227-2234.
[13]Ceremuzynski L, Budaj A, Czepiel A, et al.Low-dose glucose-insulin-potassium is ineffective in acute myocardial infarction: results of a randomized multicenter Pol-GIK trial[J].Cardiovasc Drugs Ther, 1999,13(3):191-200.
[14]Szabo Z, Hakanson E, Maros T, et al.High-dose glucose-insulin-potassium after cardiac surgery: a retrospective analysis of clinical safety issues[J].Acta Anaesthesiol Scand, 2003,47(4):383-390.
[15]Yazici M, Demircan S, Duma K, et al.Effect of glucose-insulin-potassium infusion on myocardial damage due to percutaneous coronary revascularization[J].Am J Cardiol, 2005,96(11 ):1517-1520.
[16]Shim YH, Kweon TD, Lee JH, et al.Intravenous glucose-insulin-potassium during off-pump coronary artery bypass surgery does not reduce myocardial injury[J].Acta Anaesthesiol Scand,2006,50(8):954-961.
[17]Turel B, Gemici K, Baran I, et al.Effects of glucose-insulin-potassium solution added to reperfusion treatment in acute myocardial infarction[J].Anadolu Kardiyol Derg, 2005,5(2):90-94.
[2]Mangano DT,Layug EL,Wallace A,et al.Effect of atenolol on mortality and cardiovascular morbidity after noncardiac surgery.Multicenter Study of Perioperative Ischemia Research Group[J].N Engl J Med,1996,335(23):1713-1720.
[3]Butterworth J,Furberg CD.Improving cardiac outcomes after noncardiac surgery[J].Anesth Analg,2003,97(3):613-615.
[4]Wijeysundera DN,Naik JS,Beattie WS.Alpha-2 adrenergic agonists to prevent perioperative cardiovascular complications:a meta-analysis[J].Am J Med,2003,114(9):742-752.
[5]SODI-PALLARES D,TESTELLI MR,FISHLEDER BL,et al.Effects of an intravenous infusion of a potassium-glucose-insulin solution on the electrocardiographic signs of myocardial infarction.A preliminary clinical report[J].Am J Cardiol,1962,9:166-181.
[6]Opie LH.The glucose hypothesis:relation to acute myocardial ischaemia[J].J Mol Cell Cardiol,1970,1:107-114.
[7]Kloner RA,Nesto RW.Glucose-insulin-potassium for acute myocardial infarction:continuing controversy over cardioprotection[J].Circulation,2008,117(19):2523-2533.
[8]Luna Ortiz P,Serrano Valdes X,Rojas Perez E,et al.[Metabolic support of the ischemic heart during cardiac surgery][J].Arch Cardiol Mex,2006,76 Suppl 4:S 121-136.
[9]Turel B,Gemici K,Baran I,et al.Effects of glucose-insulin-potassium solution added to reperfusion treatment in acute myocardial infarction[J].Anadolu Kardiyol Derg,2005,5(2):90-94.
[10]Ranasinghe AM,McCabe CJ,Quinn DW,et al.How does glucose insulin potassium improve hemodynamic performance? Evidence for altered expression of beta-adrenoreceptor and calcium handling genes[J].Circulation,2006,114(1 Suppl):I239-244.
[11]Tsuji H,Venditti FJ Jr,Manders ES,et al.Reduced heart rate variability and mortality risk in an elderly cohort.The Framingham Heart Study[J].Circulation,1994,90(2):878-883.
[12]Algra A,Tijssen JG,Roelandt JR,et al.Heart rate variability from 24-hour electrocardiography and the 2-year risk for sudden death[J].Circulation,1993,88(1):180-185.
[13]唐继志,方永生,孙华群,等.室性心律失常患者的心率变异性分析[J].心电学杂志,2000,19(3):134-136.
[14]戴建强,屠伟峰,张军龙,等.围术期室性心律失常与心率变异性相关性的临床研究[J].实用医学杂志,2005,21(24):2725-2726.
[15]Poldermans D,Boersma E,Bax JJ,et al.The effect of bisoprolol on perioperative mortality and myocardial infarction in high-risk patients undergoing vascular surgery.Dutch Echocardiographic Cardiac Risk Evaluation Applying Stress Echocardiography Study Group[J].N Engl J Med,1999,341(24):1789-1794.
[16]Shim YH,Kweon TD,Lee JH,et al.Intravenous glucose-insulin-potassium during off-pump coronary artery bypass surgery does not reduce myocardial injury[J].Acta Anaesthesiol Scand,2006,50(8):954-961.
[17]Lazar HL,Chipkin SR,Fitzgerald CA,et al.Tight glycemic control in diabetic coronary artery bypass graft patients improves perioperative outcomes and decreases recurrent ischemic events[J].Circulation,2004,109(12):1497-1502.
[18]施群力,吴端源,吴顺荣.强化极化液治疗心律失常╱心力衰竭121例临床观察[J]宁夏医学杂志,2000,22(12):724～726.
[19]Verma S,Maitland A,Weisel RD,et al.Hyperglycemia exaggerates ischemia reperfusion induced cardiomyocyte injury:reversal with endothelin antagonism[J].J Thorac Cardiovasc Surg,2002,123(6):1120-1124.
[20]Zarich SW.Mechanism by which hyperglycemia plays a role in the setting of acute cardiovascular illness[J].Rev Cardiovasc Med,2006,7 Suppl 2:S35-43.
[21]Umpierrez GE,Isaacs SD,Bazargan N,et al.Hyperglycemia:an independent marker of in-hospital mortality in patients with undiagnosed diabetes[J].J Clin Endocrinol Metab,2002,87(3):978-982.
[22]Robinson LE,van Soeren MH.Insulin resistance and hyperglycemia in critical illness:role of insulin in glycemic control[J].AACN Clin Issues,2004,15(1):45-62.
[23]Lewis KS,Kane-Gill SL,Bobek MB,et al.Intensive insulin therapy for critically ill patients[J].Ann Pharmacother,2004,38(7-8):1243-1251.
[24]柴长春,王占科,胡新勇,邓宏,汪仕良,李光伟.严重创伤患者胰岛β细胞功能不全与极化液临床干预效果研究[J].江西医学院学报,2005,45(5):46-49.
[25]Diaz R,Paolasso EA,Piegas LS,et al.Metabolic modulation of acute myocardial infarction.The ECLA(Estudios Cardiologicos Latinoamerica) Collaborative Group[J].Circulation,1998,98(21):2227-2234.
[26]Zuurbier CJ,Hoek FJ,van Dijk J,et al.Perioperative hyperinsulinaemic normoglycaemic clamp causes hypolipidaemia after coronary artery surgery[J].Br J Anaesth,2008,100(4):442-450.
[27]Doenst T,Richwine RT,Bray MS,et al.Insulin improves functional and metabolic recovery of reperfused working rat heart[J].Ann Thorac Surg,1999,67(6):1682-1688.
[28]Heart rate variability:standards of measurement,physiological interpretation and clinical use.Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology[J].Circulation,1996,93(5):1043-1065.
[29]全国心率变异性分析多中心研究协作组.心率变异性正常值及其重复性的多中心研究[J].中华心律失常杂志,2000,4(3):165-170.
[30]陆再英.心率变异分析方法学的标准化及结果的正确评价[J].中国心脏起搏与心电生理杂志,1996,10(4):222-224.
[31]Schwartz PJ,La Rovere MT,Vanoli E.Autonomic nervous system and sudden cardiac death.Experimental basis and clinical observations for post-myocardial infarction risk stratification[J].Circulation,1992,85(1 Suppl):I77-91.
[32]Kleiger RE,Miller JP,Bigger JT Jr,et al.Decreased heart rate variability and its association with increased mortality after acute myocardial infarction[J].Am J Cardiol,1987,59(4):256-262.
[33]Rich MW,Saini JS,Kleiger RE,et al.Correlation of heart rate variability with clinical and angiographic variables and late mortality after coronary angiography[J].Am J Cardiol,1988,62(10 Pt 1):714-717.
[34]李上共,黄元伟,朱建华,等.室性心律失常与心率变异性的相关性研究[J].心功能杂志,1999,11(1):15-17.
[35]戴建强,屠伟峰.围术期成对室早或短阵室速发生前心率变异性的动态变化[J].临床麻醉学杂志,2002,18(7):351-353.
[36]Persson PB,Wagner CD.General principles of chaotic dynamics[J].Cardiovasc Res,1996,31(3):332-341.
[37]Farrell TG,Bashir Y,Cripps T,et al.Risk stratification for arrhythmic events in postinfarction patients based on heart rate variability,ambulatory electrocardiographic variables and the signal-averaged electrocardiogram[J].J Am Coll Cardiol,1991,18(3):687-697.
[38]Bigger JT Jr,Fleiss JL,Steinman RC,et al.Frequency domain measures of heart period variability and mortality after myocardial infarction[J].Circulation,1992,85(1):164-171.
[39]Huikuri HV,Valkama JO,Airaksinen KE,et al.Frequency domain measures of heart rate variability before the onset of nonsustained and sustained ventricular tachycardia in patients with coronary artery disease[J].Circulation,1993,87(4):1220-1228.
[40]Valkama JO,Huikuri HV,Koistinen MJ,et al.Relation between heart rate variability and spontaneous and induced ventricular arrhythmias in patients with coronary artery disease[J].J Am Coll Cardiol,1995,25(2):437-443.
[1]高峰,闫文莉,张海锋,等.胰岛素抑制缺血-再灌大鼠心肌细胞凋亡及其信号转导机制[J].中华内科杂志,2003,42(03):153-156.
[2]Jonassen AK,Aasum E,Riemersma RA,et al.Glucose-insulin-potassium reduces infarct size when administered during reperfusion[J].Cardiovasc Drugs Ther,2000,14(6):615-623.
[3]Zhang HF,Fan Q,Qian xx,et al.Role of insulin in the anti-apoptotic effect of glucose-insulin-potassium in rabbits with acute myocardial ischemia and reperfusion[J].Apoptosis,2004,9(6):777-783.
[4]Zhao ZQ,Morris CD,Budde JM,et al.Inhibition of myocardial apoptosis reduces infarct size and improves regional contractile dysfunction during reperfusion[J].Cardiovasc Res,2003,59(1):132-142.
[5]Jonassen AK,Sack MN,Mjos OD,et al.Myocardial protection by insulin at reperfusion requires early administration and is mediated via Akt and p70s6 kinase cell-survival signaling[J].Circ Res,2001,89(12):1191-1198.
[6]Gao F, Gao E, Yue TL, et al.Nitric oxide mediates the antiapoptotic effect of insulin in myocardial ischemia-reperfusion: the roles of PI3-kinase, Akt, and endothelial nitric oxide synthase phosphorylation[J].Circulation, 2002,105(12): 1497-1502.
[7]Federici M, Menghini R, Mauriello A, et al.Insulin-dependent activation of endothelial nitric oxide synthase is impaired by O-linked glycosylation modification of signaling proteins in human coronary endothelial cells[J].Circulation, 2002,106(4):466-472.
[8]Das UN.Is insulin an antiinflammatory molecule?[J].Nutrition, 2001,17(5):409-413.
[9]Dandona P, Aljada A, Bandyopadhyay A.Inflammation: the link between insulin resistance, obesity and diabetes[J].Trends Immunol, 2004,25(1):4-7.
[10]Malmberg K.Prospective randomised study of intensive insulin treatment on long term survival after acute myocardial infarction in patients with diabetes mellitus[J].DIGAMI (Diabetes Mellitus,Insulin Glucose Infusion in Acute Myocardial Infarction) Study Group.BMJ, 1997,314(7093): 1512-1515.
[11]Fath-Ordoubadi F, Beatt KJ.Glucose-insulin-potassium therapy for treatment of acute myocardial infarction: an overview of randomized placebo-controlled trials[J].Circulation,1997,96(4): 1152-1156.
[12]Diaz R, Paolasso EA, Piegas LS, et al.Metabolic modulation of acute myocardial infarction.The ECLA (Estudios Cardiologicos Latinoamerica) Collaborative Group.Circulation,1998,98(21):2227-2234.
[13]Ceremuzynski L, Budaj A, Czepiel A, et al.Low-dose glucose-insulin-potassium is ineffective in acute myocardial infarction: results of a randomized multicenter Pol-GIK trial[J].Cardiovasc Drugs Ther, 1999,13(3):191-200.
[14]Szabo Z, Hakanson E, Maros T, et al.High-dose glucose-insulin-potassium after cardiac surgery: a retrospective analysis of clinical safety issues[J].Acta Anaesthesiol Scand, 2003,47(4):383-390.
[15]Yazici M, Demircan S, Duma K, et al.Effect of glucose-insulin-potassium infusion on myocardial damage due to percutaneous coronary revascularization[J].Am J Cardiol, 2005,96(11 ):1517-1520.
[16]Shim YH, Kweon TD, Lee JH, et al.Intravenous glucose-insulin-potassium during off-pump coronary artery bypass surgery does not reduce myocardial injury[J].Acta Anaesthesiol Scand,2006,50(8):954-961.
[17]Turel B, Gemici K, Baran I, et al.Effects of glucose-insulin-potassium solution added to reperfusion treatment in acute myocardial infarction[J].Anadolu Kardiyol Derg, 2005,5(2):90-94.