摘要
癫痫是最常见的慢性神经系统障碍性疾病之一,为一非特异性以脑功能异常为主的慢性脑疾病。影响到世界上近1%的人口,我国约有癫痫患者上千万,其中包括活动性癫痫约600万。现代医学的变化已使癫痫成为一种可治性疾病。由于新抗癫痫药物的不断问世,约80%的癫痫患者,通过正规的药物治疗,可以获得满意的控制,但约有120～180万的患者药物治疗效果不佳为难治性癫痫。外科治疗难治性癫痫主要通过精确定位致痫灶并切除,去除致痫因素,达到治愈的目的。
癫痫的外科治疗主要为致痫灶和癫痫病理灶的切除或传导通路切断的方法,以达到控制癫痫发作为目标。故术前对致痫灶的准确定位非常重要。现代神经影像学技术的发展为癫痫的病因、诊断定位起着重要的作用。致痫灶和功能区定位方法应根据发作症状、电生理监测和影像学综合判定。神经电生理监测技术已成为神经外科术中监测神经功能状态、减少神经损伤、提高手术疗效的重要手段。癫痫手术术中电生理监测的目的是准确寻找致痫灶,切除致痫灶是控制癫痫发作的有效措施,而精确定位则是手术成功的关键。
虽然定位方法多样,但由于脑组织在病变后的解剖移位以及个体差异,对于运动、感觉和语言区的术中定位仍以唤醒和电刺激条件下患者与医生进行交流为“金标准”。摆在麻醉医生面前的难题是如何既能保证患者的通气安全,又能在适当时候将其从麻醉状态唤醒来配合外科医生完成功能区的定位。国内外很多学者围绕通气装置、麻醉方法和麻醉药物进行了研究,但目前并没有很好的解决这些问题。针对以上问题,我们进行了如下的研究：
第一部分关于癫痫手术麻醉的研究
脑功能区手术是神经外科临床医师面临的难题之一,也是21世纪全球神经外科界要解决的重点之一。最大限度地切除病变控制癫痫发作,尽可能地保护病变周围的正常脑组织是现代神经外科发展的方向,也是脑功能区手术的新策略。为此,术中唤醒精确定位致痫灶成为手术成功的关键。
癫痫手术麻醉有一定的特殊性,特别是当需要术中唤醒进行语言功能区精确定位时,涉及到一定的特殊药物和技巧,需要高年资且有经验的麻醉医生来实施。只有这样才能做到与外科医生和患者的良好配合,共同完成手术,保护患者的功能区不受损害。
癫痫手术麻醉虽有其特殊性,但颅脑外科手术麻醉的基本原则是相同的,必须遵守的。基本原则：完善的术前准备；平稳的麻醉诱导与维持；维持心血管系统稳定和良好的脑灌注；维持呼吸道通畅和良好的呼吸功能；维持内环境平衡；控制颅内压；术后尽快平稳地清醒。
第二部分脑功能区手术术中唤醒麻醉的研究
随着影像学、微创手术技术的发展,神经外科手术也越来越细致,尤其是累及脑功能区的肿瘤、癫痫灶、血管畸形等手术,既要尽可能的切除病灶,又要最大限度的保留正常脑组织和避免神经功能的损伤,因此,精确定位脑功能区是关键。虽然定位方法多样,但由于脑组织在病变后的解剖移位以及个体差异,对于运动、感觉和语言区的术中定位仍以唤醒和电刺激条件下患者与医生进行交流为“金标准”。若全麻下气管内插管或置入喉罩通气在唤醒时均需将气管导管或喉罩拔除,待监测定位完毕后在将其重新置入,不仅有风险不安全,而且操作也十分不便,遇到如癫痫发作等紧急情况处理起来十分困难和棘手。
为提高麻醉的安全性和操作方便快捷,解决既能维持良好的通气实施全麻,又能在患者被唤醒后能发音讲话配合脑功能区定位这一难题,我们进行了系列研究,研制出食道咽腔导管(Ⅰ型)、食道鼻咽腔导管(Ⅱ型)和带吸引导管的食道鼻咽腔导管(Ⅲ型)。以上三种型号的声门上通气设备的研制成功和应用,解决了：①良好的通气效果保证了全麻的安全实施,也就是说在脑功能区手术开始和定位结束后的两个阶段能安全的使用全麻,以保证患者有足够的镇静镇痛和肌肉松弛,有条件实行手术开颅,切除肿瘤、致痫灶或血管畸形等脑内病变；②气道和发音器官未被占用,在患者清醒状态下即可发音讲话,并与医生交流,从而实现对脑功能区的精确定位,即解决了通气与讲话的矛盾；③食道被封闭避免了胃内容物的反流与误吸,并有吸引导管可防止导管侧孔被分泌物堵塞,保证导管的通畅；④操作方便简单,置管后气囊充气即可行机械通气,唤醒时排除咽部气囊中的气体,患者即可讲话,无需反复拔管插管,降低了气道控制上的风险；⑤病情发生变化时便于紧急处理,如癫痫发作时,可立即给予镇静药或肌松剂,并将气囊充气行机械通气实施全麻或其他紧急处理,极大地提高了麻醉的安全性。
右美托咪定(DEX)是强效的α2肾上腺素受体激动剂。α2肾上腺素受体主要分布在交感神经末梢和中枢神经系统的肾上腺素神经元,被刺激后可抑制去甲肾上腺素的释放。右美托咪定作为新型高选择性α2肾上腺素受体激动剂具有镇静、镇痛和抗焦虑等作用。起效快,作用时间短,兼具镇静、镇痛作用且无呼吸抑制作用是其相对于其他传统镇静药物最大的优势,右美托咪定主要作用于皮层下,不涉及γ-氨基丁酸(GABA)系统,故不损害认知功能,不干扰皮质脑电图检查结果,不影响皮质定位及功能测试,其独特的“清醒镇静”,类似于自然睡眠的非快速动眼相,患者在无外界刺激的情况下处于睡眠状态,但易被言语刺激唤醒,并与医护人员进行合作与交流,刺激消失后很快又进入睡眠状态,而且对呼吸几乎无抑制作用。目前认为DEX的镇静作用不影响功能神经外科手术中的电生理学监测。DEX还具有稳定血流动力学、抑制应激反应、减少麻醉剂及阿片类药物的用量和抗寒颤等作用。以上特点正适合于脑功能区术中唤醒。这些特性让其唤醒时间明显长于丙泊酚,不良反应明显减少,且唤醒期间血流动力学更稳定。DEX减少了呛咳和体动的发生次数,让患者在唤醒期间更舒适,同时也可减少颅内压升高和提高手术操作的安全。近年来在临床上特别是神经外科脑功能区手术麻醉中的应用越来越多。
第三部分全麻唤醒中患者能讲话的声门外通气设备的系列研制与应用
目的：研制一种脑功能区全麻唤醒手术患者可以带管讲话的声门外通气装置,使其可以应用于临床,满足脑功能区手术患者术中精确定位的需要。方法：ASA Ⅰ～Ⅱ级患者,食道咽腔导管(Ⅰ型)临床应用于妇科全麻腹腔镜手术60例,脑功能区术中唤醒麻醉10例；食道鼻咽腔导管(Ⅱ型)应用于妇科全麻腹腔镜手术60例,脑功能区术中唤醒麻醉10例；带吸引导管的食道鼻咽腔导管(Ⅲ型)应用于妇科全麻腹腔镜手术60例,脑功能区术中唤醒麻醉20例。分别观察术中通气情况,气道压、设置潮气量与实际潮气量、PETCO2、血气分析、术中BP、HR变化情况等。结果：研制的三种型号的声门上通气装置,均能达到术中唤醒后患者带管能讲话的目的,但食道鼻咽腔导管(Ⅱ、Ⅲ型)的通气效果和讲话效果均明显优于食道咽腔导管(Ⅰ型)。术中患者通气情况和血流动力学指标稳定。结论：食道咽腔导管(Ⅰ型)、食道鼻咽腔导管(Ⅱ型)和带吸引导管的食道鼻咽腔导管(Ⅲ型)均可以安全的用于脑功能区全麻唤醒手术中,食道鼻咽腔导管(Ⅱ、Ⅲ型)相比较食道咽腔导管(Ⅰ型)具有更好的通气和讲话效果。
我们计划将食道鼻咽腔导管进一步进行改进,将智能芯片植入气囊之中,可以更加方便的监测气囊的容积和压力,让麻醉医生更加直观的掌握气囊内的压力是否安全以及是否气囊发生漏气,增加安全性。
第四部分特殊的声门外通气装置—食道鼻咽腔导管的研制和使用
目的：评价自行研制能讲话的声门外通气装置—食道鼻咽腔导管的通气效果和讲话功能。方法：将6.5号气管导管的前端开口封闭,导管前端带套囊,相距8～10cm处上端带套囊,两囊之间导管上开侧孔6个。导管经鼻出后鼻孔沿咽后壁前端进入食道,侧孔开口于喉咽腔内,上下两端气囊充气后可同时封闭食道、鼻咽腔和口咽腔,导管外口与麻醉机相接。气体经导管侧孔进入喉咽腔,只能经声门进入呼吸道形成密闭的呼吸回路而实现声门外通气。临床用于宫腹腔镜探查手术全麻20例,脑功能区手术6例,观察通气和讲话效果。结果：26例置管均顺利,一次到位,漏气量0～56m1平均26±10ml,气道压12～25cmH20平均16±4cmH20,血气指标正常；讲话清晰、流利,可按指令回答各种问题。结论：食道鼻咽腔导管为一种新型带管能讲话的声门外通气装置。置管后能严密封闭食道,鼻咽腔和口咽腔,头颈活动基本不受影响,具有良好的通气效果。上端气囊放气后带管讲话吐词清晰、流利,能满足脑功能区术中唤醒,按指令发音讲话配合监测定位的需要。
第五部分右美托咪定在脑功能区癫痫病灶切除术中的应用
目的：探讨右美托咪定在脑功能区手术患者麻醉中应用的可行性,并比较在不影响脑电图及脑功能区电生理监测的情况下的适宜剂量。方法：ASA Ⅰ-Ⅱ级择期行脑功能区手术患者60例,男性34例,女性26例,年龄18～45岁,体重40～74kg,采用随机数字表法,将其随机分为4组(n=15)。对照组(C组)静脉输注生理盐水10ml/h,右美托咪定0.25μg·kg-1·h-1组(D1组),O.5μg·kg-1·h-1组(D2组)和1μg·kg-1·h-1组(D3组)。三组均于15min内静脉输注右美托咪定负荷剂量0.5μg/kg,然后分别以0.25μg·kg-1·h-1、0.5μg·kg-1·h-1或1μg·kg-1·h-1速率静脉输注右美托咪定至手术结束。术中以丙泊酚+瑞芬太尼+顺式阿曲库铵全凭静脉维持麻醉,根据BIS指数调节麻醉深度,监测开始前将丙泊酚减量并开始输注生理盐水或右美托咪定,记录术中脑电图及电生理监测的情况,术中血压、心率变化以及不良反应发生情况。结果：与C组比较,D1组、D2组和D3组的BIS值有明显降低(P<0.05)；C组脑电图波幅较高,夹杂的干扰波比较多,偶尔可见丙泊酚引起的爆发抑制；D3组脑电图较前三组波幅明显低平；D1和D2组的脑电图波幅适中。结论：作者认为脑功能区癫痫病灶切除术患者麻醉中适宜皮层脑电图(ECoG)及电生理监测的右美托咪定剂量范围是O.25μg·kg-1·h-1和0.5μg·kg-1·h-1之间,对术中脑电图及电生理监测的影响较小,比较适合于脑功能区病灶性癫痫手术术中监测时的麻醉。
第六部分右美托咪定在脑语言区全麻唤醒中的应用
目的：观察a2肾上腺素受体激动剂右美托咪定(DEX)用于脑功能语言区手术全麻术中唤醒的效果。方法：ASA Ⅰ～Ⅱ累及脑功能语言区手术患者20例,于全麻下行开颅手术,术中适时停用全麻用药,并以右美托咪定和瑞芬太尼维持,唤醒前减量至右美托咪定0.1～0.5μg/kg·h和瑞芬太尼O.05μg/kg·min维持,保持患者清醒。观察并记录清醒时间、清醒期间BP、HR、颅内压以及患者清醒讲话的清晰程度、完成指令和不良反应情况。结果：20例患者术中通气功能和血流动力学情况稳定,血气指标其中有2例PC0255-56mmHg,其余均正常,无不良反应。术后无不良记忆。发音、吐词清楚,讲话流利,均准确定位语言、视觉皮层功能区,顺利切除病灶或致痫灶,术后恢复良好,无并发症和后遗症。结论：右美托咪定不损害认知功能,不干扰皮质脑电图检查结果,不影响皮质定位及功能测试,其独特的“清醒镇静”,类似于自然睡眠的非快速动眼相,患者在无外界刺激的情况下处于睡眠状态,但易被言语刺激唤醒,并与医护人员进行合作与交流,刺激消失后很快又进入睡眠状态,而且对呼吸几乎无抑制作用。用于脑功能语言区手术全麻术中唤醒具有易调控、易唤醒,患者易配合而循环、呼吸干扰轻微的优势。
Brain regions surgery is one of the challenges faced by the neurosurgery clinical physicians, is also the focus of the21st century global nerve surgery to solve one of. Maximize the diseased control seizures, as much as possible to protect normal brain tissue around the lesion is the developing direction of modern neurosurgery, and is also a new strategy of brain functional area surgery, namely to solve lesion resection extent and patients neurologic trade-offs between to shield.Epilepsy surgery epileptogenic zone of the functional areas of the origin of tumor, should be completely removed, but the ribbon lesions, performer should not only know what place is the cutting, need to know which parts can't be cut.Therefore, intraoperative awakens the precise epileptogenic zone localization becomes the key to successful operation.
With the development of imaging, minimally invasive surgery technology, neurosurgery is becoming more and more meticulous, especially involving the functional areas of brain tumors, epilepsy, vascular malformation, such as surgery, as well as resection of lesions, as much as possible to retain maximum normal brain tissue and to avoid the damage of nerve function, therefore, accurate positioning brain regions is the key.Although locating method is diversiform, but as a result of brain tissue after lesion anatomy shift and individual differences, to movement, sensory and intraoperative localization of language area still to awaken and electrical stimulation under the condition of patients and doctors to communicate as the gold standard. If under general anesthesia endotracheal intubation or placement laryngeal mask airway when wake up, all needs to pull out the endotracheal tube or laryngeal mask, waiting for monitoring and positioning to end in the placement, not only has not safe risk, and the operation is very inconvenient, encounter emergencies such as seizures in a difficult and difficult to handle.In order to improve the safety of anesthesia and convenient operation, and solve the implementation of the general anesthesia can maintain good ventilation, and can be awakened in patients after pronunciation speech cerebral function positioning this problem, we conducted a series of research, developed the pharyngeal cavity catheter (Ⅰ) of the esophagus, esophagus, nasopharyngeal cavity catheter (Ⅱ) and attract catheter nasopharyngeal cavity catheter (Ⅲ) of the esophagus. All three types of ventilation equipment, the successful development and application of the glottis, solved:(1) Good ventilation effect to ensure the implementation of the safety of the general anesthesia, that is to say, in the brain regions after the start and operation of two stages to the safety of general anesthesia, to ensure that patients have enough sedation analgesia and muscle relaxation, conditional execute surgical craniotomy, epileptogenic zone resection of tumor, or brain lesions such as vascular malformation;(2) The airway and pronunciation organs non-hold in patients awake can speak pronunciation, and communicate with the doctor, so as to realize accurate positioning of brain regions, which solved the contradiction between ventilation and speech;(3) The esophagus is a closed to avoid the reflux and aspiration of gastric contents, and attract the catheter can prevent the tube side hole is plugged, discharge to ensure that the catheter unobstructed;(4) Convenient operation simple, catheter balloon inflated is feasible after mechanical ventilation, wake expel gas in pharyngeal airbags, patients can talk, don't need to repeatedly drawing tube intubation, reduce the risk of airway control;(5) Condition changes for emergency treatment, such as seizures, can be an immediate sedatives or nondepolarizing agent, the mechanical ventilation and airbag filling line implement general anesthesia or other emergency treatment, greatly improved the safety of anesthesia.
Dexmedetomidine (DEX) is powerful alpha2agonists adrenaline.Alpha2adrenergic receptor mainly distributed in the sympathetic nerve endings and adrenaline neurons of the central nervous system, after being stimulated can inhibit the release of norepinephrine.Its microphones set right as a new selective alpha2agonists adrenaline has sedative and analgesic and anti anxiety, and so on. Work fast, time is short, both sedative and analgesic action and no respiratory inhibition is its greatest advantage compared with other traditional sedative drugs, dexmedetomidine under fixed role mainly in cortex, does not involve gamma-aminobutyric acid (GABA) system, so does not harm the cognitive function, not interfere with the cortical eeg examination results, will not affect the cortex localization and function test, its unique "conscious sedation", similar to the nature of non-rem sleep, in the case of no stimulation in patients with sleep state, but easy to be awakened verbal stimuli, and cooperation and communication with medical staff, stimulate go off to sleep again, and almost no inhibition for breathing.Now think of DEX sedation does not affect the electrophysiological monitoring functional neurosurgery.DEX also has stable hemodynamics, restrain stress reaction, reduce the dosage of anesthetic and opioids and chills, and so on.The above characteristics are suitable for the brain functional areas in awakening.These features make the wake up time is significantly longer than propofol, adverse reactions decreased significantly, and more stable hemodynamics during the wake up.DEX reduces the choking cough and the number of the happening of the body to move, let patients more comfortable during the wake up, it also can reduce intracranial pressure and improve the safety of the operation.In clinic, especially in recent years more and more application of dexmedetomidine were used during neurosurgical brain regions anesthesia.
The Esophageal nasopharyngeal catheter which is a Ventilation equipment that can speech outside the ventilation device.
Objective: To evaluate the self-developed to address the noise outside the ventilation equipment-Ventilation ducts of esophageal nasopharynx effects and speech function. Methods: No.6.5endotracheal tube of the front opening closed catheter tip with Cuff,8～10cm away from the top office with a cuff, the conduit between the two capsule on the open side of6holes. Catheter through the nose after the nose to the posterior pharyngeal wall, front-end into the esophagus, the side openings in the hypopharyngeal cavity, the upper and lower ends may also be closed after the balloon inflated esophagus, nasopharynx and oropharynx, catheter outside the mouth and the anesthesia machine to connect. Gas catheter side holes into the hypopharyngeal cavity, can only be formed through the glottis into the respiratory tract to achieve a closed breathing circuit and ventilation. Clinical anesthesia for laparoscopy in20cases, brain areas anesthesia in6cases, observed effects of ventilation and speech. Results:26patients with catheter smoothly, once in place, gas leakage0-56ml, an average of26±10ml, airway pressure of12-25cmH2O, an average of16±4cmH20. Blood gas analysis, normal, clear speech, fluent, can answer questions in accordance with instructions. Conclusion: Esophageal nasopharyngeal catheter is a new sound with a tube to the speech outside the ventilation device. After the catheter can be tightly closed esophagus, nasopharynx and oropharynx, the basic activity is not limited head and neck, with good ventilation effect, when the upper airbag exhaust the speech with the word spit clear, fluent in the language areas of brain function can meet Intraoperative wake-up, according to the needs of the speech pronunciation instruction.
The application of dexmedetomidine in the anesthesia of the brain functional areas surgery.
Objective: Study the feasibility of the application of dexmedetomidine in the anesthesia of the brain functional areas surgery, and compare the appropriate dosage that neither affect electroencephalogram nor brain functional areas electrophysiological monitoring. Methods:60patients with ASA Ⅰ-Ⅱ selective cerebral functional area surgery, male34cases, female26cases, ages18to45years old,40～74kg weight. Using the random number table method, the random is divided into four groups (n=15). The control group (group C) intravenous injection saline10ml/h, the dexmedetomidine group intravenous injection respectively0.25μg·kg-1·h-1(group D1),0.5μg·kg-1·h-1(group D2),1μg·kg-1·h-1(group D3). Three groups of intravenous loading doses within15min. And then respectively with the rate0.25μg·kg-1·h-1、0.5μg·kg-1·h-1or1μg·kg-1·h-1until the end of surgery by intravenous infusion. Intraoperative propofol, remifentanyl, cis-atracurium by vein to maintain anesthesia, according to the BIS index to adjust the depth of anesthesia,reducing propofol and starting the saline or dexmedetomidine infusion before monitoring. Records of electroencephalogram and electrophysiological monitoring of the situation, the dosage of propofol, remifentanyl, cis-atracurium, recovery times, the changes of blood pressure, heart rate and the occurrence of adverse reactions intraoperative. Results: Compared with group C, Dl, D2and D3group BIS value has significantly decreased (P<0.05); ECoG of group C is higher, the inclusion of the interference wave is more, sometimes visible propofol caused the outbreak of the inhibition; ECoG from the previous three groups amplitude D3group was obviously low;D1and D2set of ECoG amplitude is moderate. Conclusion: Brain function lesion resection in patients with epilepsy in anesthesia appropriate ECoG and electrophysiological monitoring right beautiful mi fixed dose range is O.25μg·kg-1·h-1and0.5μg·kg-1·h-1, more suitable for the brain functional areas of focal epilepsy surgery anesthesia.
The clinical use of dexmedetomidine in the wake-up surgery of brain function language areas.
Objective: To observe the effects of the α2adrenaline receptor agonists-Dexmedetomidine (DEX) used in the wake-up surgery of brain function language areas. Methods:There were20patients of ASA Ⅰ～Ⅱ the brain function language area surgery with general anesthesia. During the operation, timely discontinuation the use of anesthesia drugs, and only use the Dexmedetomidine0.1～0.2ug/kg·h and Remifentanyl0.05ug/kg·min to maintain, then wake up the patients and keep patients awake. Observation the awake time and the BP, HR, intracranial pressure, the clarity of the speech, the effects of complete instructions and adverse reaction. Results:All the20cases were awaked in10min after discontinuation the use of drugs with clear and smooth speech, complete instructions, no obvious adverse reaction. And the operation effects were good. Conclusions:Dexmedetomidine used for the brain function language area of intraoperative awaken general surgery with the advantage of easy to control and awaken, the patients' good cooperation, slight circulation and respiratory disturbance.
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