【作者】 秦海林；

【导师】 马廉亭；

【作者基本信息】 南方医科大学 ， 神经外科学， 2014， 博士

【摘要】 开颅去骨瓣减压术(decompressive craniectomy,DC)是缓解经保守治疗无效、持续升高颅内压力(intracranial pressure,ICP)最终有效的手段,尤其是额颞顶骨瓣(又称“外伤标准大骨瓣”)近十几年成为神经外科研究的热点之一,在多个国家、多个临床中心开展了系统的临床研究。大量研究证明,开颅去大骨瓣减压是恶性颅内压增高的有效缓解手段,能提高重型颅脑损伤、大面积脑梗塞及其他重症脑血管疾病等患者的生存率、缩短住院时间、减少住院经费、降低致残率,并写入了美国和部分欧盟国家的急性颅脑损伤救治指南。该手术方式于上世纪末,在我国神经外科尤其是神经创伤领域得到了较广泛的推广使用。颅内压是指颅腔内容物(脑组织、循环的脑脊液和血液)对颅腔壁产生的压力,它由液体静力压和血管动脉压两个因素所构成。正常成年人在侧卧平静呼吸时从腰椎穿刺或平卧时侧脑室内测得的压力约为0.8～2.0kPa (80～200mmH20),儿童为0.5～1.0kPa(50～110mmH20).正常颅内压是保证中枢神经系统内环境稳定和执行各种神经生理功能的必要条件,颅脊腔是一个近似于密闭的骨性结构,当颅腔内容物体积增加超过颅内代偿(正常为颅腔容积的8-10%),颅内压就会升高,超过颅腔所能代偿空间的极限时,就会出现颅内压急剧升高,如得不到及时、正确的处理,大脑或小脑的某一部分,由于受到压力的推挤而发生移位,被挤到颅内附近阻力较小的生理孔道或非生理孔道,如天幕裂孔、枕骨打孔或大脑镰下,使部分脑组织、神经及血管受压,脑脊液循环和血液循环发生障碍产生相应的症状群,这一危及病人生命的紧急情况谓之“脑疝综合征”,简称“脑疝”,将会造成严重继发性脑损害,甚至危及生命。颅内压升高可见于急性颅脑损伤、颅内肿瘤、颅内炎症、脑寄生虫病、脑血管疾病、中枢神经系统中毒、发育畸形以及各种原因所造成的脑缺氧、脑水肿等神经系统疾病。降低颅内压主要有药物治疗和外科手术治疗,临床上神经外科很多危重患者药物保守治疗不能得到缓解,需要开颅手术进行病因治疗如清除颅内血肿、切除肿瘤、切除或纠正畸形等；另外一部分病人,脑组织水肿、颅内压恶性升高,需去除骨瓣增加颅腔容积,给脑组织一个缓冲的空间,降低颅内压。目前为广大神经外科医师接受的去骨瓣手术原则为骨瓣面积尽量大、骨窗尽量靠近颅底。但是,是不是骨瓣面积越大越好呢?有一部分学者提出了疑问,认为大骨瓣减压也可能导致较多的并发症或后遗症,比如脑组织嵌顿、脑软化、脑室穿通畸形、神经传导纤维扭曲变形、生活质量下降等。而且,骨瓣越大、创伤越大、手术时间越长、出血越多,对急性颅脑损伤患者尤其是合并有其他系统损伤或其他基础疾病患者影响较大,可能影响患者预后；另外,后期行颅骨修补术过程中,手术时间、出血量、材料面积均增加,增加了患者的负担,也可能影响手术的效果。特别是2011年发表于新英格兰医学杂志上的随机对照研究认为早期去骨瓣对弥漫性脑损伤预后没有帮助,反而增加了并发症的机会。虽然其试验设计、开颅标准受到了不少专家的批评,但对去骨瓣减压在重型颅脑损伤患者中的应用提出了挑战。那么,开颅去骨瓣减压前后颅内压的演变过程是怎样的?颅骨骨瓣面积大小与降低颅内压力之间到底存在何种关系、骨瓣的位置或形状与颅内压力下降之间有什么关联?去骨瓣减压没有达到理想的效果是否与骨瓣面积大小有关?因去骨瓣减压后扩大了颅腔容积、改变了颅腔容积与颅内容物体积之间的比例关系,可否用原来的正常颅内压数值去衡量、去骨瓣减压后多少压力是其正常值?目前尚缺乏较系统的研究。本课题进行开颅去骨瓣模型的实验研究和临床试验,主要探讨去骨瓣后颅内压力的演变过程、颅腔顺应性改变及颅骨骨瓣面积、位置形状与颅内压力下降之间的关系,希望能找到可能存在的面积-压力公式,给临床开颅去骨瓣减压术提供一定的参考。本课题分为以下两个部分进行研究：第一部分实验研究：利用外形和容积大小与成人颅骨相似的模型建立颅内压研究模型,根据不同的位置、不同面积骨瓣及不同的初始压力分组,用颅内压探头动态测定去骨瓣前后颅内压力,然后绘制压力-容积曲线,探讨压力变化、颅腔顺应性与骨瓣位置、面积及颅内初始压力之间的关系。第二部分临床试验：选取弥漫性脑水肿颅内压持续升高的患者进行开颅去骨瓣减压手术,颅内压探头动态测定去骨瓣前后、硬脑膜剪开后及术后24h压力,探讨开颅去骨瓣后颅内压的演变过程,研究骨瓣面积、部位与压力下降之间的关系,探讨去骨瓣减压、颅内压监测在重型颅脑损伤患者处理中的作用。第一章颅骨去骨瓣后颅内压变化及颅腔顺应性改变的实验研究目的：在成人头颅模型中模拟手术过程去骨瓣,监测颅内压力变化、绘制压力-容积曲线,了解去骨瓣对颅内压力及颅腔顺应性或代偿功能的影响。方法：取正常成年男性尸头颅骨颅内荧光标记后激光扫描,获得人头颅骨三维数据后建模,利用高级树脂材料做成人头颅骨模型,神经孔均用柔软的树脂材料封闭,同时用无弹性材料封堵枕骨大孔；颅内容物利用装满稀释造影剂的聚乙烯囊代替,囊内固定位置(相当于室间孔位置)放置颅内压探头(美国Codmam公司生产)自枕骨大孔引出,外接颅内压监护仪动态监测颅内压力。向里灌注稀释造影剂至平枕骨大孔,作为初始模型。将一侧颅骨表面规律分成网格状,每一格为10mm×10mm大小,用以计算去骨瓣面积。首先向预先放置的气囊内注入稀释造影剂,记录注入物体积与压力并绘制曲线,检验是否符合“容积-压力曲线”。实验根据骨瓣位置、初始压力及骨瓣面积分组。第一组为颞顶瓣组,骨瓣面积大小设计10个(分别为26、32、37、42、47、56、76、95、113、131cm2),每个大小的骨瓣分别在5、11、15、20、30、40、50毫米汞柱初始压力值(分别相当于68、150、204、272、408、544、680毫米水柱颅内压力)情况下去骨瓣,颅骨表面贴附硅胶膜,类似于去骨瓣后缝合的头皮,每组均测定去骨瓣前后压力,同时每个骨瓣去除后缓慢增加颅内容物容积,观察压力-容积变化,了解颅内压急剧升高切点(Abrupt point)所对应的颅内容物体积,对比不同面积骨瓣代偿容积及颅腔顺应性变化；第二组为单纯额瓣、第三组为单纯枕顶瓣组,实验方法同第一组,但是因为额骨、枕骨面积较小,骨瓣设计受限制,面积分组只有8组(26、32、37、42、47、56、76、95cm2)。数据读取主要为压力显示值及压力-容积曲线切点处颅腔代偿容积。结果：模型内注满稀释造影剂后初始压力为3mmHg,容积为1120mm1,未去骨瓣时当颅内容物增加60m1时压力开始上升,但上升很缓慢,90m1后开始随着颅内容物体积增加压力急剧升高。颞顶瓣不同面积(26、32、37、42、47、56、76、95、113、131cm2)对应的切点处代偿容积分别为100ml、105ml、110ml、115ml、120ml、127ml、140ml、155ml、156ml、158ml,额瓣不同面积骨瓣(26、32、37、42、47、56、76、95cm2)对应的切点处代偿容积分别为85ml、89ml、94ml、99ml、105ml、112ml、120ml、133ml,顶枕瓣不同面积骨瓣(26、32、37、42、47、56、76、95cm2)对应切点处代偿容积分别为98ml、103ml、108ml、113ml、120ml、128ml、140ml、156ml。三种骨瓣切点代偿容积与骨瓣面积呈正相关,其中颞顶瓣面积与代偿容积间简单线性回归方程为y=81.10+0.79b,决定系数R2=0.99；额瓣面积与代偿容积间简单线性回归方程为y=69.32+0.69b,决定系数R2=0.98；顶枕瓣为y=77.86+0.84b,决定系数R2=0.99(y值为代偿容积、b为骨瓣面积、a为常量,所有a、b值p<0.01)。颞顶瓣边界超过顶结节后代偿容积随面积升高趋势明显减缓。在不同的压力值去骨瓣后测颅内压力,不同面积的骨瓣压力下降结果：25mmHg以下每个面积的骨瓣都可以使颅内压下降到基础压力值,30mmHg以上随着骨瓣面积的增大可以逐渐降至基础压力值。颅腔密闭时颅内压50mmHg,减少内容物5ml,压力可以迅速下降至3-5mmHg。结论：本实验的颅骨模型压力-容积曲线与Cushing绘制的压力-容积曲线基本一致。在颅腔内容物容积保持不变的情况下,去骨瓣能迅速有效的降低颅内压；压力较高的情况下,骨瓣越大,降压效果越明显。颅骨去骨瓣后颅腔的压力-容积曲线均发生不同程度的改变,面积越大,曲线沿横轴右移越明显,代偿容积越大,颅腔的顺应性越强,但是颞顶瓣超过顶结节后减压效果下降。单纯的额瓣减压效果较颞顶瓣、顶枕瓣可能稍差。压力较高的情况下,不去除骨瓣,减少内容物体积也能降低颅内压。第二章重型颅脑损伤患者去骨瓣减压前后颅内压演变的临床研究目的：通过测定开颅去骨瓣减压术前术后的压力变化,了解去骨瓣后颅内压的病理生理改变,探讨开颅去骨瓣减压手术与颅内压下降之间的关系,研究去骨瓣减压、颅内压监测在重型颅脑损伤患者治疗中的作用。方法：选取14例重型颅脑损伤需行开颅去骨瓣减压手术患者,主要病情为弥漫性脑肿胀或弥漫性轴索损伤,病情严重或神经功能障碍持续加重,去骨瓣前将颅内压监护仪探头置入监测颅内压力,分别测定去骨瓣前压力、去骨瓣后压力、硬脑膜剪开后压力、术后24h颅内压力,各组压力之间行使用重复测量方差分析进行处理,以p<0.05为差异有统计学意义；计算每个骨瓣面积,并与该患者各时期颅内压力变化做比较,进行Pearson相关分析及简单线性回归,计算相关系数和回归方程,分析骨瓣面积与压力下降百分比之间关系；随访6月进行预后评分(Extended Glasgow outcome scale,GOSE).结果：全部14例患者均顺利进行颅内压监护仪探头置入及开颅去骨瓣减压术,去骨瓣前、去骨瓣后、硬脑膜剪开后、术后24h压力分别为38.9±6.2mmHg.22.5±3.3mmHg.6.8±2mmHg、12.2±3.7mmHg,与术前压力比较去骨瓣当时、硬脑膜剪开后、术后24h压力分别下降41.3±9.3%、81.6±7.8%、67.2±12.6%,均p<0.01。压力下降百分比与骨瓣面积均呈正相关,去骨瓣当时、硬脑膜剪开、术后24h比术前压力下降百分比与骨瓣面积简单线性回归方程及决定系数分别为y=17.18+0.26b R2=0.65、y=59.97+0.24b R2=0.76、y=35.58+0.35b R2=0.50(y代表降压百分比、b代表骨瓣面积,p<0.01)。6月后随访患者3例死亡,2例植物生存,2例恢复不良(GOSE评分2-4分),7例恢复良好(GOSE评分(Extended Glasgow outcome scales)5-8分)。结论：开颅去骨瓣减压能有效缓解恶性颅内压增高,面积越大,代偿空间越大,减压效果越明显；硬脑膜剪开后压力下降明显,提醒开颅去骨瓣减压手术中需充分剪开硬脑膜减张缝合；颅内压监护仪能适时反映颅内压力高低,对病情观察及治疗方案的制定、预后判断有一定的指导意义；去骨瓣减压在重型颅脑损伤中所起作用仍需要多中心、大样本、前瞻性随机对照研究来证实。今后的研究方向需完善去骨瓣减压术的各项指标、探讨脑水肿发生机制及脑水肿靶向药物的研制。更多还原

【Abstract】 Part1Experimental study on intracranial pressure after decompressive craniectomyObjective:To observe variations of intracranial pressure (ICP) pre and post decompressive craniectomy(DC), and to investigate the impact of DC on ICP alteration and the cranial compliance.Methods:The surgical procedure of DC was operated on the adult skull mold, ICP was monitored, and the pressure-volume curve was plot.Results:The initial ICP of the mold filled with diluted contrast was3mmHg, and the baseline volume was1120ml. The ICP began to rise slowly below60ml of additional cranial contents, but the ICP rose sharply above90ml of additional cranial contents. Temporal-parietal bone flaps of different sizes (26332,37,42,47,56,76,95,113,131cm2) generated different abrupt-point related volume:100ml,105ml,110ml,115ml,120ml,127ml,140ml,155ml,156ml,158ml. Frontal bone flaps of different sizes (26,32,37,42,47,56,76,95cm2) generated lower abrupt-point related volume:85ml,89ml,94ml,99ml,105ml,112ml,120ml and133ml respectively. But parietal-occipital bone flaps of different sizes (26,32,37,42,47,56,76,95cm2) generated nearly the same abrupt-point related volume as98ml,103ml,108ml,113ml,120ml,128ml,140ml, and156ml respectively. After different sizes of decompressive craniectomy at different levels of intracranial pressure, ICP decreased rapidly. While below25mmHg nearly every bone flap could reduce ICP to baseline which is3mmHg. When the ICP was above30mmHg, larger bone flaps led to greater ICP decrease. When the intracranial pressure was higher than40mmHg,5ml of cranial volume could make ICP drop sharply to3-5mmHg.Conclusion:The pressure-volume curve of model was in accordance with the physiological pressure-volume curve basically. DC could quickly and effectively reduce ICP; Under high ICP, larger bone flap produced larger compensatory volume and greater decline of intracranial pressure; The pressure-volume curve altered after decompressive craniectomy. The larger the bone flap was, the pressure-volume curve shifted more obviously to the right along the horizontal axis, and more compensatory cranial volume was gained, accordingly the cranial compliance was better. However, the decompressive effect decreased when the temporal-parietal bone flap was beyond the parietal tuber. The decompressive effect of the simple frontal bone flaps was poorer than temporal-parietal flaps or the parietal-occipital flaps. When the ICP was high, mini-loss of intracranial volume could gain great decrease of ICP.Part2Clinical study on variations of intracranial pressure after decompressive craniectomy in severe traumatic brain injury Objective:To study the pathophysiology variation of ICP after decompressive craniectomy (DC) in severe traumatic brain injury (TBI), and to explore the relationship between ICP alteration and DC. To identify the roles of decompressive craniectomy and intracranial pressure monitoring in the procedure of treating patients with severe traumatic brain injury.Methods:Fourteen patients with severe traumatic brain injury gained fronto-tempo-parietal DC or tempo-parietal DC. The pre-operation states included diffuse brain swelling or diffuse axonal injury with severe disability or deteriorating neurological disorders. The ICP was monitored before and after DC, right after the dura opening, and24h after DC. The survivors were followed up by structured telephone interview and the outcomes were ranked by GOSE (Extended Glasgow outcome scales, GOSE). We defined unfavorable outcomes as patients with scales5-8and unfavorable outcomes with scales1-4.Results:All the14patients got the operations of ICP transducer-probe implantation and decompressive craniectomy. The ICP before craniectomy, after craniectomy, right after dural opening, and24h after DC were38.9±6.2mmHg,22.5±3.3mmHg,6.8±2mmHg,12.2±3.7mmHg respectively. Six months later, Patients were followed up and ranked by GOSE (Scales1for three, Scales2for two, Scales2-4for two and Scales5-8for seven). That was,3died,2at vegetable state,2disabled and7with common life.Conclusions:Decompressive craniectomy could effectively reduce the malignantly increased intracranial pressure. The larger the bone flap was, the greater the compensatory space was got, and the decompressive effect was more obvious. Because ICP decreased significantly after the Dura opening, the Dura should be expanded completely to reduce ICP and gain more compensatory space. Monitoring of ICP was beneficial for the treatment of patients with severe traumatic brain injury, and may predict favorable outcome. As to what is the role of Decompressive Craniectomy in the treatment of sTBI, it is controversial, so more randomized controlled tests (RCT) are need to carry out. And also more efforts should be put into the study of the mechanism of cerebral edema and the exploration of new medicine.更多还原