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局部脑氧饱和度监测的临床应用进展

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  摘    要:大脑是人体能量代谢最活跃、需氧及耗氧量最大而氧储备量最小的器官,对缺氧环境比较敏感,短暂缺氧即可造成不可逆的中枢神经系统损伤。近年来近红外光谱(near-infrared spectroscopy, NIRS)技术可以监测额叶皮质脑组织局部脑氧饱和度(regional cerebral oxygen saturation, rScO2)的变化,通过脑组织微脉管水平(其中包括了25%小动脉、70%小静脉和5%毛细血管)的血氧饱和度来反映脑组织氧的供需平衡情况,判断脑缺血的发生。基本原理主要是根据Beer-Lambert定律,即光线在溶液中的通透性取决于溶液中可吸收分子的密度(浓度)及光波的波长。在很多诊疗过程中都存在着脑组织灌注不足的风险,诊疗过程中如果患者出现rScO2下降则发生神经系统并发症如神经心理功能障碍、脑卒中、认知功能障碍等风险将显著增加。由于NIRS技术监测rScO2操作简单、无创,可以进行连续监测而广泛应用于临床。此技术较常规监测指标有更高的灵敏度和特异度,故更有利于保障患者脑功能安全,减少神经系统并发症的发生。文章结合近年国内外最新研究,分析NIRS技术监测rScO2的实用性及准确性,介绍NIRS技术监测rScO2的基本原理、围术期应用新进展以及未来展望、心肺复苏、新生儿领域应用及影响因素。推广其在诊疗过程中高危人群的应用,以减少神经系统并发症,改善患者预后,使其在临床工作中发挥更大的功效。

  

  关键词:脑氧饱和度 监测 临床应用

  

  Research progress on the clinical application of monitoring brain oxygen saturation

  

  ZHANG Feng GAO Yilong GAO Jingui

  

  Department of Anesthesia,The Second Hospital of Hebei Medical University;

  

  Abstract:The brain is the organ with the most active energy metabolism, the highest oxygen demand and oxygen consumption, and the lowest oxygen reserve, and it is sensitive to the hypoxia environment, and transient hypoxia can cause irreversible central nervous system damage.In recent years, near-infrared spectroscopy(NIRS) can monitor the changes of regional cerebral oxygen saturation(rScO2) in frontal cortex, and reflect the balance of oxygen supply and demand in brain tissue by blood oxygen saturation of cerebral microvascular level(including 25% arterioles, 70% venules and 5% capillaries) to judge the occurrence of cerebral ischemia.The basic principle is mainly based on the Beer-Lambert law, that is, the permeability of light in a solution depends on the density(concentration) of absorbable molecules in the solution and the wavelength of the light wave.During the diagnosis and treatment, there exists a risk of insufficient brain tissue perfusion, if patients have a decline in rScO2,the risk of neurological complications including neuropsychological dysfunction, stroke, cognitive dysfunction, will significantly increase.NIRS technique for monitoring rScO2 is widely used in clinical practice because it is easy to operated and non-invasive, allowing continuous monitoring.Based on the latest research grogress in home and abroad, this article analyzes the practicability and accuracy of NIRS technology in monitoring rScO2,introduces the basic principle of NIRS technology in monitoring rScO2,the new progress and future prospect in perioperative application, the application of cardiopulmonary resuscitation, and in neonate department as well as its influencing factors, so as to promote its application in high-risk groups to decrease the neurological complications and improve the prognosis of patients, and make it play a greater role in clinical practice.

  

  Keyword:brain oxygen saturation; monitoring; clinical application;

  

  大脑中枢是维持生命和意识的重要器官,也是人体代谢最为活跃、需氧和耗氧量最大而氧储备量最小的器官。正常情况下,成人脑组织重量约1 400 g, 仅占体重的2%,但安静状态下的血流量却占心输出量的15%,相当于每100克脑组织50~70 ml/min, 耗氧量约占全身的20%,因此脑组织对缺氧缺血的耐受性极差。根据相关文献报道,在脑损伤致死的患者中,>90%的患者出现了脑组织的缺氧缺血[1]。临床工作中维持脑组织的氧供需平衡是其中重要的目标之一。近年来近红外光谱(near-infrared spectroscopy, NIRS)技术监测局部脑氧饱和度(regional cerebral oxygen saturation, rScO2)是一种新型的脑氧饱和度监测方法。此技术可持续监测rScO2且灵敏度高、不受脉搏搏动和温度等因素影响[2],在心脏外科、神经外科、胸外科、新生儿、心肺复苏等领域都有广泛应用[3-5]。本文主要就NIRS技术监测rScO2的基本原理和在临床应用进行综述。

  

  1 NIRS技术的基本原理

  

  在公元1800年英国科学家弗里德里希·威廉·赫歇尔(Friedrich Wilhelm Herschel, 1738~1822年)第一次提出了红外线的观点。根据波长可将其分为近红外线、中红外线和远红外线。其中,近红外线的波长约为700~1 000 nm[6]。在此波长范围内,光线能够穿透人体组织,例如皮肤、皮下组织、骨骼、血管等。而当光的波长>1 000 nm时,水对光的吸收显著,光线不能有效穿透人体组织;当光的波长<600 nm时,吸收及散射问题导致光线无法穿透生物组织[7],这一特点在无创rScO2监测中起到了关键性作用。

  

  近红外光线在颅内的衰减主要与氧合血红蛋白(HbO2)、还原血红蛋白(Hb)和细胞色素aa3等发色基团有关,而每种发色基团对近红外线的吸收都有特殊性[4]。我们可以根据光学方法将HbO2和Hb区分开来。当近红外光线穿透人体组织后,HbO2和Hb对近红外光线有不同程度的吸收作用,我们测量从组织中射出红外线的发光强度,然后再根据修正比尔-朗伯(Beer-Lambert)定律,就可得出rScO2的数值,即rScO2=HbO2/(Hb+HbO2)[8]。rScO2是由25%~30%的动脉血成分、70%~75%的静脉血成分和一部分毛细血管加权后得出的混合静脉血的血氧饱和度。NIRS技术监测rScO2与反映大脑氧代谢的金标准——颈静脉球血氧饱和度有很好的相关性[9],可以连续反映脑组织的氧供需平衡状况。

  

  2 NIRS在外科手术中的应用

  

  2.1 在心脏外科手术中应用

  

  NIRS技术监测rScO2已经在心脏外科手术中应用甚广。有研究显示,术中rScO2降低的严重程度与术后神经系统并发症的发生率、住院天数和术后认知功能障碍(postoperative cognitive dysfunction, POCD)之间存在明显的相关性[10-15]。Orihashi等[16]对59例行选择性脑灌注(SCP)主动脉手术患者进行了脑氧饱和度监测,发现有27.1%的患者出现了神经系统并发症,其中有6例为新发脑梗死患者,并发症患者rScO2下降的时间和手术的时间明显大于无并发症者,研究结果还表明主动脉手术中rScO2的持续下降与术后神经系统并发症密切相关。朱凯等[17]研究也验证了这一见解。Adams等[18]选取了200例行冠状动脉旁路移植术(GABG)患者进行了随机对照研究,发现术中rScO2的基础数值和平均数值越低,术后患者滞留在ICU的时间和术后总住院时间均明显延长。随之Fisher等[13,19]研究也同样证实在心脏手术中rScO2降低的幅度与停留在ICU的时间和住院时间呈正相关。Schoen等[14]对rScO2在心脏手术中是否预测POCD发生进行了研究,结果显示体外循环心脏手术中POCD的发生和低rScO2有关。但也有研究发现在心脏瓣膜手术中rScO2与POCD的发生并没有相关性[20]。所以,在心脏手术中rScO2的变化是否与POCD相关目前仍存在争议。

  

  NIRS技术监测rScO2除用于评估心脏手术预后外,还可指导手术操作及治疗。有研究提示,使用NIRS技术监测rScO2作为心脏瓣膜手术患者特定管理算法的一部分可以减少不必要的输血并降低医疗成本[21]。另有研究显示,心脏手术中,监测rScO2可以提示动静脉插管对位是否正确,帮助术中及时调整和矫正动静脉插管的位置[22,23]。Orihashi等[24]选取了35例行主动脉弓手术患者进行rScO2监测,其中4例患者单侧或双侧rScO2值出现了明显的下降,及时准确的提示了选择性脑灌注导管的位置放置错误,制止了因为脑血流降低产生的严重并发症。

  

  2.2 在神经外科手术中的应用

  

  神经外科手术中人体可能产生剧烈的应激,从而引起交感神经兴奋,致使脑组织水肿的发生和颅内压的增加,最终降低脑组织灌注,轻者可增加手术难度和造成POCD的发生,重者可引起脑疝甚至危及生命[25,26]。因此围术期监测脑功能状态非常重要。NIRS技术不仅能监测脑氧代谢情况,还能降低围术期脑血管意外的发生率[27]。

  

  颅脑损伤患者由于脑组织水肿的发生和颅内压的升高,继而导致脑血流下降、脑组织缺血缺氧,从而产生不可逆性脑损伤,影响患者预后[28]。脑氧饱和度监测对脑组织缺氧十分敏感。Dunham等[29]在一项研究中对4例重型颅脑创伤的患者进行持续6 d的脑灌注压(CPP)和脑氧饱和度的监测,发现rScO2和CPP密切相关,当rScO2≥75%时,96.4%的时间CPP≥70 mm Hg(95%CL,94.3%~98.5%),提示脑灌注良好,而当rScO2<55%时,68.2%的时间CPP<70 mm Hg(95%CL,57%~79.4%),提示脑灌注不足。此项试验显示NIRS技术可以作为一种测量颅脑损伤患者脑灌注的监测工具。唐剑等[30]也同样发现,脑氧饱和度与脑灌注压呈正相关。rScO2值降低幅度越大提示患者病情状况越严重,能敏感地反映脑氧代谢情况并及时判断预后。

  

  目前容易引起缺血性脑卒中的常见疾病为颈内动脉狭窄或闭塞,治疗这类患者常用的外科方法是颈动脉内膜剥脱术(CEA)[31]。研究表明术中连续应用NIRS监测rScO2技术能够有效预防CEA相关的围术期死亡与卒中的发生[32]。Samra等[33]研究发现,利用rScO2下降的界值(较基础值下降20%)来识别CEA围术期脑缺血的发生情况时,其预测脑缺血事件的特异性是82%,敏感性是80%,阴性预测值为97.4%。表明利用rScO2下降界值可排除CEA术中没有发生脑缺血事件的人群。另有报道指出,NIRS技术可指导CEA术中是否需要放置分流管。若将rScO2较基础值降低16%作为阈值评判CEA术中的脑缺血事件,其阳性预测值较低,而阴性预测值高达99%,结果显示NIRS技术可除外不需要放置分流管的患者[34]。虽然各研究数据结果不同,但一般认为脑氧饱和度下降相对值>12%,是具有一定敏感性和特异性的脑缺血指标,并且对CEA术中是否需放置分流管具有指导意义[35]。也有相关文献显示CEA术中rScO2监测可作为术后脑高灌注(CHS)指标[36]。Ogasawar等[37]研究发现,以rScO2较基础值升高5%作为阈值检测CEA术后CHS事件的发生,其敏感性和特异性均>86%。因此,术中rScO2监测可辨别CEA术后容易发生CHS的人群。但也有研究发现,rScO2较基础值升高>10%可作为CHS的独立危险因素之一[38]。因此,CEA术中rScO2预测CHS的阈值目前结论不一。

  

  2.3 在胸外科手术中的应用

  

  胸外科手术中常需要进行单肺通气(OLV),患侧胸腔被打开后,由于大气压的作用空气进入该侧胸腔,该侧胸腔负压消失,肺的弹性回缩使该侧肺部分萎缩导致肺的通气和气体交换面积急剧减少,尽管肺萎陷和缺氧可产生缺氧性肺血管收缩(HPV),但这种代偿机制有限,且HPV常受到麻醉药物、扩血管药物等的抑制,患者仍然存在肺通气/血流比值失衡风险,并且手术中需要侧卧位叠加OLV的病理生理改变最终导致肺泡和动脉氧张力的降低,可能导致低氧血症的发生。有研究表明,胸科手术OLV期间发生脑组织低灌注发生的概率为80%[39]。Brinkman等[40]对23例胸科手术行OLV患者进行了前瞻性观察性研究,发现在OLV期间rScO2会显著降低,同时行血气分析发现,动脉血氧分压显著低于基础值,然而在rScO2降低期间,测得的心率、血压、脉搏血氧饱和度、呼末二氧化碳等常规监测指标均在正常范围内。Tang等[41],发现患者氧分压在手术开始时为411 mm Hg, 而在OLV时竟下降到188 mm Hg, rScO2值也从79%降至63%,进一步证明胸科手术OLV期间会有明显的rScO2降低,同时发现患者POCD的发生与术中rScO2下降有显著相关性。

  

  Casati等[42]也发现在胸科手术OLV期间,大部分患者的rScO2有不同幅度的降低,并与POCD有明显的相关性。有报道指出以术中rScO2低于基线值的10%作为阈值,预测POCD发生的敏感度为90%,特异度为86.5%,并且指出rScO2可作为POCD发生的重要预测因子[43]。有数据表明,若以基础值的65%作为临界值,OLV期间rScO2低于临界值的患者术后发生非呼吸器官衰竭的可能性是未低于临界值患者的2.37倍,发生并发症的概率是3.19倍[44]。因此rScO2监测在胸外科手术OLV期间很有必要。

  

  2.4 在其他手术中的应用

  

  在肩部手术中常常采用沙滩椅体位,该体位有更好的手术视野,减少了出血的风险,但这一体位由于重力作用使心排血量减少、平均动脉压和脑灌注压降低,致使脑缺血的风险明显提高,可能产生严重的神经系统并发症。研究发现,当患者从仰卧位换成坐位时,rScO2明显下降并且持续处于较低的水平[45]。Murphy等[46]发现肩关节镜手术中,与侧卧位的手术对比,当患者取沙滩椅体位时rScO2会出现明显的下降,并且在沙滩椅体位中有多数患者的rScO2会低于55%。曾有文献报道在行沙滩椅体位的手术患者中出现了严重神经系统的并发症,甚至出现了死亡的病例[47]。术中连续应用NIRS监测rScO2依然是可以预防脑灌注不足、防治脑缺血的方法。

  

  Casati等[42]对100多例行腹部手术患者进行了干预性研究,入组患者均应用NIRS技术监测rScO2,其中试验干预组rScO2值维持在>75%的基础值,而对照组只进行rScO2的监测。术后随访对照组的住院时间和POCD发生率明显高于干预组。另有一项研究发现,46例行腹部大手术的老年患者中有11例患者术中rScO2下降幅度>20%,其中6例患者rScO2的下降与术中出血密切相关[48]。由此可见,行腹部手术患者术中应用NIRS监测rScO2,可实时、连续监测患者的脑氧状态,便于术中及时调整,减少围术期神经系统并发症。

  

  Kim等[49]对行脊柱手术的老年患者展开了rScO2的相关研究,发现术中rScO2的下降程度及持续时间与术后第7天POCD发生率明显相关。Papadopoulos等[50]发现行髋关节置换手术患者术前rScO2及术中rScO2的变化与术后认知功能下降及住院时间显著相关。对围术期患者应用NIRS监测rScO2,可减少POCD的发生。

  

  3 NIRS技术在新生儿的应用

  

  新生儿期是非常独特的,因为婴儿在从子宫内到子宫外的生命过渡期间发生了剧烈的生理变化,这一过程涉及血流动力学的改变,影响氧合,且新生儿脑部发育不完善,对缺氧和高氧非常敏感[6],容易发生缺血缺氧性脑病(HIE),此时期监测rScO2极其重要。车伟坤等[51]等对86例新生儿患者进行了随机对照研究,其中观察组为明确诊断为HIE的患儿,对照组为相同时间段出生的无合并HIE的患儿,研究结果提示观察组HIE患儿出生后3 h、12 h、48 h的rScO2值均低于对照组,而2组患儿出生后3 h、12 h、48 h的脉搏血氧饱和度比较无统计学差异。说明了单纯检测脉搏血氧氧饱和度是无法准确判断机体局部组织的氧合情况,即使检测出的脉搏血氧饱和度处于正常范围[52]。

  

  Sokoloff等[53]研究中对20例新生儿患者进行了脑氧饱和度的监测,并且将患儿在惊厥发作时和口服抗惊厥药物后的rScO2值进行了对比,发现患儿在惊厥发作时,脑氧饱和度较基线下降明显,而在使用苯巴比妥后,脑氧饱和度较基线明显回升,表明惊厥可能增加患儿脑组织的耗氧量,研究结果表明NIRS技术可以用于监测新生儿惊厥的异常生理信息,但在药物评估临床效果方面尚待进一步的研究。在对380例早产患儿rScO2监测的一项研究中,发现患有严重动脉导管未闭的患儿其动脉导管直径的变化与rScO2的变化密切相关,随着动脉导管的闭合,rScO2会逐步升高,而未能闭合的患儿rScO2一直保持较低的数值[54]。

  

  对于新生儿,基于NIRS技术的监测深度和新生儿肝脏及肾脏等组织到体表距离小的特点,其可直接监测婴幼儿肝肾等组织氧饱和度,为评估重要脏器氧供提供了一种新的监测方法[55]。有研究报道,先天性心脏病患儿手术后发生坏死性肠炎的婴儿肠道氧饱和度更低,且在25%量喂养时肠道氧饱和度值<30%的次数更多[56]。另有报道指出,NIRS技术可监测早产儿出生后脑血流自主调节功能状态及脑氧饱和度的情况,为及早预防脑损伤和评估神经系统预后提供参考[57]。同时,NIRS监测技术还可评估新生儿大脑的反应性[58,59]。总而言之,NIRS监测rScO2技术为新生儿提供了一种安全无创的脑组织血氧监测的方法。

  

  4 NIRS技术在心肺复苏中的应用

  

  在心脏骤停(cardiac arrest, CA)后最容易发生缺血、缺氧性损伤的器官是脑组织,超过黄金5 min可能造成大脑严重损伤或死亡,即使复跳成功也可能遗留不同程度的后遗症。因此,从20世纪60年代开始,就把“心肺复苏”发展成“心肺脑复苏”,将心脏骤停后患者脑功能的恢复作为心肺复苏成败的关键。Cournoyer等[60]对20项非随机观察性研究进行了meta分析,发现自主循环恢复(return of spontaneous circulation, ROSC)与rScO2平均值之间存在明显的相关性(SMD=1.33,95%CI=0.92~1.74),并且将长时间rScO2值<30%作为停止复苏的指征,说明rScO2可作为临床指标用于评价心肺复苏。

  

  Turk等[61]对20例CA患者进行了观察性研究,心肺复苏期间连续记录rScO2值,应用四评分法评估幸存者的神经系统状态、疾病严重程度和器官功能障碍程度。结果发现20例患者中有8例发生了ROSC。存活者rScO2的最大值高于非存活者(P<0.05)。rScO2的最小值和平均值与幸存者1周四评分呈正相关(r=0.811,r=0.771,P=0.015,P=0.025)。提示rScO2的最大值影响ROSC,而rScO2最小值和值影响CA患者后的神经预后。对心脏无脉电活动、心搏停止和心室颤动/心动过速患者实施CPR,rScO2与ROSC亦呈正相关性[62-64]。但也有报道不支持该结论[65]。因此,心肺脑复苏期间rScO2和患者预后的相关性有待进一步研究。

  

  5 NIRS监测rScO2的影响因素

  

  由于电极片放置位置不当或不正确的操作而得到的NIRS信号会严重影响我们术中对rScO2监测的准确性,并且不能保证监测到的数据只是rScO2而不受头皮或头骨内血流的影响。另外,近红外光不能穿透探头和组织之间的气体和出血层,所以在硬膜外、硬膜下以及脑组织中有出血或颅内积气时会影响监测结果[6]。以往研究表明年龄、血红蛋白浓度、氧合血红蛋白浓度、呼气末二氧化碳浓度、心排量及血容量对大脑氧饱和度都有影响[66]。Sun等[67]提出皮肤的色素沉着对NIRS监测也有影响,黑人的脑氧饱和度普遍低于白种人。同时造影剂也对NIRS监测有干扰,吲哚青绿会使脑氧饱和度读数升高,而亚甲蓝会导致脑氧饱和度读数降低[68]。脑氧饱和度是通过近红外光线测得,因而rScO2监测还受光学途径长度相关因素影响,如颅骨厚度、差分路径长度及模具脑脊液层的面积等,均会影响脑氧饱和度的数值[69]。

  

  综上所述,NIRS技术监测rScO2在心脏手术、神经外科手术、胸外科手术、新生儿、心肺复苏等领域应用甚广,能够及时监测脑组织的氧供需平衡情况及脑血流的动态变化,及早对脑组织缺血、缺氧做出评价,指导术中麻醉管理,可以减少术后并发症的发生率,尤其是神经系统并发症和POCD的发生,缩短住院时长,改善患者预后。随着对NIRS技术的理解提高,未来可通过NIRS监测rScO2计算脑血流的调节能力和脑氧代谢情况,更直观、详细的指导脑保护,因此NIRS监测rScO2这项技术应用于围术期麻醉监测具有广泛的临床应用前景。

  

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