成人缺血缺氧性脑病预后的相关因素研究

广州医学院2009级硕士学位论文成人缺血缺氧性脑病预后的相关因素研究Prognosis Factors Research In Adult Patients With Hypoxic-Ischemic Encephalopathy专业名称：神经病学研究方向：脑血管病学位申请人：林哲聪导师：高聪教授广州医学院·广州2012年5月目录中文摘要 (1)英文摘要 (5)前言 (9)第一部分成人HIE患者的临床特点及其预后影响因素分析 (12)临床资料与方法 (12)结果 (15)第二部分成人HIE患者脑功能监测及临床预后的评价意义 (18)临床资料与方法 (19)结果 (20)讨论 (26)结论 (33)展望 (34)英文缩写 (35)附图 (36)参考文献 (39)致谢 (43)学位论文原创性声明 (44)成人缺血缺氧性脑病预后的相关因素研究研究生：林哲聪导师：高聪教授专业：神经病学广州医学院神经科学研究所广州医学院第二附属医院广州市昌岗东路250号（510260）中文摘要缺血缺氧性脑病(Hypoxic-Ischemic Encephalopathy HIE)是心肺复苏术抢救成功后极其严重的并发症，可造成患者致命性的伤害，同时也给患者家庭及社会带来沉重的经济负担。

尽管脑复苏在心肺复苏指南中占据重要的地位，然而目前仍无较好的治疗手段对其进行有效的预防与治疗。

亚低温治疗是目前被认为的最有可能用于成人HIE特别是中、重度HIE的治疗方法，但亚低温的实施必须在一定的时间窗(事件发生后6小时内)内进行，因此寻找能够辅助早期临床诊断成人HIE尤其是中、重度成人HIE的敏感指标具有重大意义。

经颅彩色多普勒(Transcranial Doppler TCD)、动态脑电图(Active Electroencephogram AEEG)及脑干听觉诱发电位(Brainstem Auditory Evoked Potential BAEP)是近年来发展起来的适用于重症患者的脑功能监测手段，有助于临床早期发现HIE并判断其严重程度，然而国内尚未在成人HIE应用中进行相关研究。

脑血流动力学异常与脑血流自主调节功能受损是缺血缺氧性脑病主要的病理生理基础。

心跳、呼吸骤停进行心肺复苏后的昏迷患者 (脑弥漫性缺血缺氧性损害 )很难通过临床表现评估病情和判断其临床预后,根据心脏停搏时间、呼吸停止和昏迷持续时间的判断亦并非精确可靠。

另外，患者在进行多功能心电监护、呼吸机辅助治疗或氧治疗、药物治疗或液体维持时,不方便搬动甚至不能离开重症病房，CT和 MRI等影像学检查因此受到限制。

而TCD、动态脑电图及BAEP作为脑功能重要的监测与评估技术,对缺血缺氧性脑功能损害极其敏感 ,床旁操作简单易行,可重复检测或长程监测。

关于成人HIE预后的影响因素分析及综合应用TCD和动态脑电图对成人HIE患者脑功能损伤程度及临床预后预测，目前国内极少研究报道。

本课题旨在通过探讨（1）成人HIE临床特点及其影响因素，以利于早期对危险因素进行早期干预。

（2）TCD、动态EEG监测技术在成人HIE的价值，对病情严重程度及临床预后评估的意义，寻找出成人HIE的脑功能监测比较有价值的手段及指标。

第一部分成人HIE患者的临床特点及其预后的影响因素分析【目的】分析成人缺血缺氧性脑病的临床特点及其预后的影响因素【方法】对2010年5月至2011年12月间在我院中心ICU住院的未发生缺血缺氧性脑病对照组60例患者及60例发生HIE的成人患者进行临床资料收集并行临床特点分析、采用Logistic回归模型分析成人HIE患者临床预后与相关的影响因素的关联。

总结各种临床指标及检验结果对患者临床预后的影响。

【结果】 1.成人HIE组中高血压病史、卒中病史、糖尿病史及冠心病史的病例数明显多于未发生HIE对照组，差异有统计学意义(P<0.05)。

2.Logistic回归显示高血压病史、冠心病史、糖尿病史、卒中病史、血白细胞、血红蛋白、白蛋白、血肌酐、血氧分压、血乳酸均为成人HIE患者临床预后的影响因素。

第二部分成人HIE患者脑功能监测【目的】综合评价TCD、动态EEG及TCD联合动态EEG在成人HIE病情严重程度判断及临床预后评估中的价值。

【方法】对60例成人HIE患者进行TCD、动态脑电图监测，并进行严重程度的分级及临床预后的随访，将Glasgow评分、TCD、AEEG及TCD联合监测结果与患者病情严重程度、临床预后进行相关分析，比较各自对预测临床预后的敏感性、特异性、准确率及错误率。

【结果】1. TCD监测显示成人HIE患者早期即存在脑血流的低阻力及高灌注现象，表现为Vs、Vm、Vd数值增高和PI及RI数值降低。

2. TCD监测结果显示各脑血流速度参数数值、PI及RI数值与成人HIE患者脑功能损害程度存在相关性：即脑血流速度越快，成人HIE患者出现重度脑功能损伤的可能性越大；PI、RI数值越低，成人HIE患者出现重度脑功能损伤可能性也越大；其中Vm，RI与各自参数数值相关性更强，可成为较好的监测指标。

3. 动态脑电图分级结果显示：I和II级动态EEG大部分成人HIE患者可达到临床完全恢复，临床预后良好。

III级动态EEG的临床预后差, 其中只有1例（1.7%）完全恢复, 2例（3.3%）留有部分神经系功能障碍, 7例（11.7%）始终处于植物状态, 2（3.3%）例死亡。

IV、V级的临床预最差，其中有9例（15%）处于植物状态，7例（11.7%）死亡。

由此提示成人HIE患者的临床预后与动态EEG的分级严重程度相关。

其中III级可认为一分界标准。

4.利用ROC曲线分析显示：Glasgow评分曲线下面积为0.868，其敏感性为76.7%，特异性80.0%，准确率78.3%，错误率为10.0%；Glasgow评分+动态脑电图曲线下面积为0.980，其敏感性为93.1%，特异性90.3%，准确率91.7%，错误率为5.0%。

5.Glascow评分与Glasgow评分+动态脑电图之间就其敏感性、特异性、准确率、错误率进行比较率的比较结果显示：Glasgow评分联合动态脑电图在成人HIE 患者临床预后判断中其敏感性、特异性、准确率均明显高于单一GLasgow评分及单一动态脑电图，而错误率明显低于GLasgow评分。

差异均有显著性(P<0.05)。

【结论】1. 心脑血管病史、糖尿病史是成人HIE患者的影响因素。

2. 血乳酸、血肌酐、血白细胞等生化指标是影响成人HIE患者临床预后的重要指标。

3. TCD对HIE患者的病情严重程度及临床预后的判断有一定价值。

其中Vm，RI 是较好的监测指标。

4. Glasgow评分联合动态EEG监测对成人HIE早期病情判断及临床预后评价比单一Glasgow评分及单一动态EEG更具临床实用意义。

【关键词】成人缺血缺氧性脑病，经颅彩色多谱勒，动态脑电图Prognosis Factors Research In Adult Patients With Hypoxic-Ischemic EncephalopathyGraduate: Lin ZhecongAdvisor: Professor Cong GaoInstitute of Neuroscience, 2nd Affiliated Hospital of Guangzhou Medical College Guangzhou,510260,P.R.ChinaAbstractThe disease of HIE is the most serious complication when recovering from cardiopulmonary resuscitation, is vital harm for patients, will bring with heavy burden for society. Although brain resuscitation takes over important status in guideline of CPR, there is no better way to finish brain resuscitation effectively. Recently mild hypothermia therapy has been very effective measure to be applied with HIE especially for moderate or severe HIE, however, mild hypothermia therapy must be implemented within window of time (within six hours). So looking for sensitive index is necessary for clinical doctors to help with diagnosing moderate or severe HIE early. Transcrnial and electroenphogram is a recently developed technique, which is suitable for the monitoring of neonatal cerebral function. It could predict the severity and neurological outcome of HIE. There is no related study for adult patients with HIE available in China up to now.The impaired cerebral autoregulation and hemodynamics are the primary pathophysiologic mechanisms of brain injury in HIE. It is difficult for judging and assessing state and prognosis of patients who suffer CPR and it is not very exact only according to time of cardiac arrest and lasting time of coma. In other hand, The examination of CT、MRI usually been limited because it is not convenient and moved for patients when they are inintensive care unit. TCD、AEEG has many advantages for monitoring cerebral function in adult patients with HIE, which is they are sensitive, easily operate, its mobility, its repeatability and its sustainability. There are few studies about the combined application of these techniques and analyze high risk factors in adult HIE.The study is designed:1.to analyze clinical features different from control group,look for high risk factors of HIE2.to investigate techniques of TCD and AEEG were applied in HIE,to assessthe effect of TCD and AEEG on early diagnosis brain injury and prediction of long outcome in adult HIE. The objective is to seek most valuable method for cerebral function and judging prognosis in adult patients with HIE.Part One Clinical Features Analyzing And Seeking Influencing Factors For Adult Patients With HIE[Objective] To study clinical features in adult patients with HIE, and seek high risk factors, it would provide some evidences for treat with HIE early.[Method]Sixty patients without happening HIE and sixty patients with HIE were collected from intensive care unit of the second hospital affiliated Guangzhou medical college. All clinical data were assembled and were analyzed between May in 2010 and October in 2011. We also analyzed the correlation between high risk factors and prognosis of patients with HIE. Finally, we analyzed how clinical index and examination results influenced prognosis of patients with HIE by logistic method. [Results] 1. The ratio of the history of hypertension、stroke、diabetes and coronary disease is higher in HIE group than control group, which has significant difference between them (P<0.05).2.The result indicate from logistic analyzing that indexes of white cell count、Hb、ALB、CREA、POand LAC are influencing factors for HIE happening.2Part Two Cerebral Function Monitoring In Adult Patients With HIE [Objective]To assess value of brain injury and its prognosis by combined application of TCD、dynamic EEG in adult patients with HIE. [Method] Sixty patients with HIE were monitored by TCD and dynamic EEG，all patients were scored by Glasgow standard and then keep following with outcome of all patients. The results of Glasgow score、TCD and dynamic EEG were compared about sensitivity and specificity between the two groups.[Results] 1. The results from TCD monitoring showed that adult patients with HIE were in a state of low resistance and high perfusion early after HIE, the value of Vs、Vm、and Vd was increased and value of PI and RI was decreased.2. The cerebral blood velocity about Vs、Vm、Vd and PI、RI has relevance with extent of brain injury, the results indicated that the higher about value of cerebral blood velocity and lower about value of PI、RI, the more impossible about severe brain injury in adult patients with HIE.3. The classification level from dynamic EEG results showed that most of patients with HIE could get rehabilitation completely if level I and level II in dynamic EEG monitoring. The clinical prognosis was poor in level III of EEG monitoring. Only one patient could get rehabilitation and two patients leaved over neurological function disorder, seven patients were in a state of vegetable, and two patients had died. The prognosis was the poorest about level IV and V of dynamic EEG monitoring. Nine patients were in a state of vegetable and seven had died. We could find from exact data it was closely related between level of EEG and clinical outcome.4. The area under the cure about Glasgow score was 0.868, the sensitivity was percent of 76.7, specificity was percent of 80.0, exactness ratio was percent of 78.3, and fault ratio was percent of 10.0; the area under the cure about Glasgow scoring combined dynamic EEG monitoring was 0.980, the sensitivity was percent of 93.1, specificity was percent of 90.3, exactness ratio was percent of 90.6, and fault ratio was percent of5.0 by using ROC cure analyzing.5. The test result of ⅹ2 method indicated that the sensitivity、specificity and exactness ratio about Glasgow scoring combined dynamic EEG monitoring were higher than used by Glasgow scoring, however, the fault ratio was lower, which was significant difference between them for judging clinical outcome(P<0.05).[Conclusions]1. The history of heart and cerebral diseases and diabetics is promoting factors in patients with HIE.2. The white cell count、CREA、LAC and so on are important indexes for influencing prognosis of patients with HIE.3. TCD is valuable for monitoring severity of illness and clinical prognosis for patients with HIE, however, Vm and RI are better indexes during monitoring.4. The monitoring method of Glasgow scoring combining with active EEG is more clinical practice meaningful for applying with estimate severity of illness and clinical prognosis than the method of single Glasgow scoring or dynamic EEG.[Key Words] Adult Hypoxic-Ischemic Encephalopathy(HIE)，Transcrnial Doppler(TCD)，Active Electroencephogram(AEEG).前言缺血缺氧性脑病(HIE)是心肺复苏术抢救成功后(ROSC)最常见和严重的并发症。