第二军医大学学报  2017, Vol. 38 Issue (4): 515-519   PDF    
引用本文
陈荣彬, 魏嘉良, 董艳, 王君玉, 韩凯伟, 于明琨, 黄承光, 侯立军. 开颅血肿清除联合脑室外引流治疗高血压脑出血破入脑室的疗效[J]. 第二军医大学学报, 2017, 38(4): 515-519  
CHEN Rong-bin, WEI Jia-liang, DONG Yan, WANG Jun-yu, HAN Kai-wei, YU Ming-kun, HUANG Cheng-guang, HOU Li-jun. Curative effect of hematoma evacuation combined with external ventricular drainage in treatment of patients with intraventricular hemorrhage secondary to hypertensive intracerebral hemorrhage[J]. Academic Journal of Second Military Medical University, 2017, 38(4): 515-519 (in Chinese with English abstract)  
开颅血肿清除联合脑室外引流治疗高血压脑出血破入脑室的疗效
陈荣彬, 魏嘉良, 董艳, 王君玉, 韩凯伟, 于明琨, 黄承光, 侯立军     
第二军医大学长征医院神经外科, 上海 200003
收稿日期: 2016-10-14    接受日期: 2017-02-27
基金项目: 国家自然科学基金（81371382），上海市"领军人才"计划（2012049），上海市科技人才计划（15XD1504700）.
作者简介: 陈荣彬, 博士生.E-mail:crb2588@163.com
通信作者(Corresponding author): 侯立军, Tel:021-81886811, E-mail:HouLJsmmu1968@163.com
摘要: 目的 探讨开颅血肿清除联合脑室外引流和单纯脑室外引流治疗高血压脑出血破入脑室的疗效。 方法 回顾性分析2012年6月至2015年6月3年内我院收治的70例接受手术治疗的高血压脑出血破入脑室患者的临床资料，其中脑室外引流联合开颅血肿清除（EVD+HE组）患者31例，单纯脑室外引流（EVD组）39例。比较两组患者的格拉斯哥昏迷评分（GCS）、神经外科重症监护室（NICU）住院天数、死亡率、肺部感染、颅内感染和再出血的发生率以及随访6个月后的改良Rankin量表（mRS）评分及格拉斯哥预后评分（GOS）。然后筛选比较两组中幕上血肿量>30 mL患者的上述临床指标。 结果 术后住院期间EVD+HE组9例（29.0%）患者死亡，EVD组2例（5.1%）死亡，差异有统计学意义（P=0.008）；其余存活患者继续纳入后续研究。EVD+HE组患者GCS评分增加值（ΔGCS）大于EVD组（P < 0.05）；两组患者NICU住院时间，术后再出血及肺部感染、颅内感染发生率，随访6个月后mRS及GOS评分的差异无统计学意义（P>0.05）。EVD+HE组幕上血肿量>30 mL的患者ΔGCS、术后6个月mRS及GOS评分均优于EVD组（P < 0.05），但NICU住院时间、术后再出血及肺部感染、颅内感染发生率与EVD组相比差异无统计学意义（P>0.05）。 结论 对于幕上血肿量>30 mL的患者，开颅血肿清除联合脑室外引流术疗效优于单纯脑室外引流术。
关键词: 脑出血     高血压     脑室外引流     脑室内出血     血肿清除    
Curative effect of hematoma evacuation combined with external ventricular drainage in treatment of patients with intraventricular hemorrhage secondary to hypertensive intracerebral hemorrhage
CHEN Rong-bin, WEI Jia-liang, DONG Yan, WANG Jun-yu, HAN Kai-wei, YU Ming-kun, HUANG Cheng-guang, HOU Li-jun     
Department of Neurosurgery, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China
Supported by National Natural Science Foundation of China (81371382), "Leading Talent" Project of Shanghai (2012049), and Scientific and Technological Talent Project of Shanghai (15XD1504700).
Abstract: Objective To investigate the curative effects of hematoma evacuation (HE) combined with external ventricular drainage (EVD) and simple EVD in the treatment of patients with intraventricular hemorrhage secondary to hypertensive intracerebral hemorrhage (HICH). Methods We retrospectively analyzed the clinical data of 70 patients who were diagnosed with HICH from Jun. 2012 to Jun. 2015 in Changzheng Hospital of Second Military Medical University. The patients were divided into EVD combined with HE group (EVD+HE group, n=31) and EVD group (n=39) according to the different choices of operation. The Glasgow Coma Scale (GCS) score, length of neurointensive intensive care units (NICU) stays, in-hospital mortality, incidences of lung infection, intracranial infection and rebleeding, and modified Rankin Scale (mRS) scores and Glasgow Outcome Scale (GOS) scores after 6 months were compared between two groups. Then we screened the patients with supratentorial hematoma volume greater than 30 mL in the EVD+HE group (n=20) and EVD group (n=13), and compared the above clinical indicators between two groups. Results The in-hospital mortality rate of patients in the EVD+HE group was significantly higher than that in the EVD group (29.0% vs 5.1%, P=0.008). The survival patients were included in the subsequent research, including 22 cases in the EVD+HE group and 37 in the EVD group. The improved GCS (ΔGCS) scores of survival patients in the EVD+HE group was significantly higher than that in the EVD group (3.9±3.5 vs 1.2±3.3, P < 0.05). The length of NICU stays, incidences of lung infection, intracranial infection and rebleeding, and mRS scores and GOS scores after 6 months of survival patients were not significantly different between the EVD+HE group and EVD group (P>0.05). After screening, the patients with supratentorial hematoma volume greater than 30 mL in the EVD+HE group had significantly higher improved GCS (ΔGCS) scores (3.8±4.0 vs 1.1±2.4, P=0.044), lower 6-month mRS scores (4.2±1.6 vs 5.3±0.7, P=0.025) and higher 6-month GOS scores (3.1±2.0 vs 1.7±0.7, P=0.030) than those in the EVD group. The length of NICU stays, incidences of rebleeding, lung infection and intracranial infection of patients were not significantly different between the EVD+HE and EVD groups (P>0.05). Conclusion For patients with supratentorial hematoma volume greater than 30 mL, HE combined with EVD is superior to simple EVD in treating intraventricular hemorrhage secondary to hypertensive intracranial hemorrhage.
Key words: cerebral hemorrhage     hypertension     external ventricular drainage     intraventricular hemorrhage     hematoma evacuation    

高血压脑出血是最常见的出血性脑卒中，发病率高，致死和致残率高，给患者家庭及社会带来严重的经济负担[1~3]。高血压脑出血破入脑室主要见于丘脑及基底节出血，发生率为30%~40%，患者预后差[4~5]。脑室外引流 (external ventricular drainage，EVD) 是治疗脑室出血的常用术式，既往研究表明EVD能加速脑室内血肿的溶解吸收，降低脑室出血患者的致死率和致残率[6~9]。而开颅血肿清除 (hematoma evacuation，HE) 是清除脑实质内血肿最直接的方式，但高血压脑出血破入脑室患者是否需行开颅HE仍存争议，接受开颅HE能否使幕上脑出血患者获益仍为争议的焦点。脑出血手术治疗试验 (STICH) 表明，与保守治疗相比，接受开颅HE治疗并未使深部脑血肿患者获益[10]。因此高血压脑出血破入脑室的患者在行EVD的基础上是否需要联合开颅HE仍有待研究。本研究旨在探索开颅HE联合EVD是否可以使高血压脑出血破入脑室患者受益。

1 资料和方法 1.1 研究对象

研究对象为2012年6月至2015年6月于第二军医大学长征医院神经外科确诊为高血压脑出血破入脑室的患者152例。入选标准：既往明确高血压病史，符合美国心脏协会和美国卒中协会 (AHA/ASA) 发布的美国成人自发性脑出血治疗指南 (2015) 的诊断标准[6]，血肿量采用多田公式计算；CT诊断血肿位于丘脑或基底节并破入脑室；无双瞳散大等晚期脑疝表现，无双侧脑室同时出血铸型，无CTA提示动脉瘤、血管畸形或肿瘤卒中引起的出血；无颅脑损伤病史，无凝血功能障碍 (包括口服抗凝药、抗血小板药或有明显的肝肾功能不全患者)。根据选择手术方式的不同分为EVD联合开颅HE (EVD+HE) 组及单纯EVD组，并对两组中幕上血肿量>30 mL患者的临床资料进行分析。

1.2 治疗方案

所有患者术前完成头颅CT检查及格拉斯哥昏迷评分 (GCS)，药物控制收缩压、舒张压分别于140~160 mmHg (1 mmHg=0.133 kPa)、90~100 mmHg，使用凝血酶或维生素K肌注促凝血，20%甘露醇静滴、呋塞米静注缓解颅内高压。侧脑室出血量超过50%，且幕上血肿量>30 mL或入院时幕上血肿量≤30 mL、CT复查时见血肿扩大，GCS评分下降2分以上者需行EVD+HE。侧脑室出血量超过50%，入院时幕上血肿量≤30 mL、但经保守治疗血肿未见扩大的患者行单纯EVD。EVD手术步骤：采用额角穿刺，以冠状缝前2 cm、中线旁开2.5 cm处为穿刺点，穿刺方向对准双侧外耳孔假想连线并与矢状位平行，一次性颅内穿刺针穿入侧脑室额角，依次连接引流管和引流袋，拔出针芯见血性脑脊液流出。开颅HE手术步骤：根据血肿体积在颞部选择合适的骨窗大小，采用直视下或内镜辅助方式，尽量在保护正常脑组织的前提下清除基底节区血肿，认真止血。所有手术均由长征医院主治医师以上资历医师进行。术后转入神经外科重症监护室 (NICU)，加强内科治疗及专科护理措施，12 h内待病情稳定后复查头颅CT。侧脑室引流瓶床边高度距离外耳道约10~15 cm，控制每日脑脊液引流量约150 mL，观察脑脊液每日引流量及颜色、性状。术后3 d、7 d及出院前常规复查头颅CT，若患者突然出现意识下降，脑脊液引流量突然增加伴随鲜血引出者随时复查。定期随访，随访形式有门诊复查、电话随访、书面随访。

1.3 疗效评估

收集患者一般资料、临床及影像学相关数据。主要疗效终点：手术前后GCS变化 (ΔGCS；ΔGCS=术后GCS－术前GCS)、NICU住院天数、肺部感染发生率、颅内感染发生率和出血复发率。次要疗效终点：随访6个月后改良Rankin量表 (mRS) 评分和格拉斯哥预后评分 (GOS)。

1.4 统计学处理

应用SPSS 19.0软件进行数据分析。计量资料以x±s表示，两组间比较采用Student’s t检验；计数资料采用百分比表示，组间比较采用χ2检验。检验水准 (α) 为0.05。

2 结果 2.1 患者术前一般资料分析

本研究入选高血压脑出血破入脑室患者共152例，其中50例采用保守治疗，32例失联或拒绝随访，故纳入研究的患者共70例。男性47例，女性23例；年龄18~75(52.5±14.3) 岁。临床表现以头痛起病者59例 (84.3%)，发生呕吐者30例 (42.9%)，并发癫疒间者4例 (5.7%)，术前昏迷者5例 (7.1%)。接受EVD+HE治疗的患者31例，接受单纯EVD治疗的患者39例。两组患者年龄、性别、血压、发病至手术时间及出血部位的差异无统计学意义 (P>0.05)。与EVD组相比，EVD+HE组术前血肿量较大 (P=0.013)，且GCS评分较低 (P=0.040)。见表 1。

表 1 两组患者的一般资料

2 2两组患者的术后疗效及随访情况

术后住院期间EVD+HE组9例 (29.0%) 患者死亡，EVD组2例 (5.1%) 死亡，差异有统计学意义 (P=0.008)；两组其余患者纳入后续研究：EVD+HE组22例，EVD组37例。与EVD组相比，EVD+HE组术后GCS评分的提升较高 (P=0.009)。两组患者的NICU住院时间和肺部感染、颅内感染、术后再出血发生率的差异均无统计学意义；随访6个月后，两组患者mRS和GOS评分差异均无统计学意义。见表 2。

表 2 两组患者术后疗效对比

2.3 幕上血肿量＞30 mL患者一般资料的比较

筛选幕上血肿量＞30 mL的患者，其中EVD+HE组20例，EVD组13例，对两组患者的一般资料进行分析，两组差异无统计学意义。见表 3。

表 3 两组幕上血肿量＞30 mL患者的一般资料

2.4 两组幕上血肿量＞30 mL患者术后疗效的比较

术后住院期间EVD+HE组4例 (20.0%) 幕上血肿量＞30 mL患者死亡，EVD组1例 (7.7%) 死亡，两组差异无统计学意义 (P=0.625)；其余幕上血肿量＞30 mL患者纳入后续研究：EVD+HE组16例，EVD组12例。术后EVD+HE组患者的GCS评分的提升较EVD组高 (P=0.044)。与EVD组相比，随访6个月EVD+HE组幕上血肿量＞30 mL患者的GOS评分升高 (P=0.030)，mRS评分降低 (P=0.025)。见表 4。

表 4 两组幕上血肿量＞30 mL患者术后疗效对比

3 讨论

本研究结果显示EVD联合开颅HE的患者术后GCS评分的提升较高，但同时伴院内死亡率较高。值得注意的是，本研究中两组患者的术前GCS评分与颅内血肿量基线水平不一致，而血肿量、GCS评分亦是影响高血压脑出血患者预后的关键因素[11~12]。为减少两组的选择偏倚，我们对幕上血肿量＞30 mL且基线一致的患者进行分析，结果显示EVD+HE组患者的ΔGCS评分的提升高于EVD组患者，随访6个月后预后指标GOS评分较高，而mRS较低，差异均有统计学意义 (P＜0.05)。因此，我们认为对于幕上血肿量＞30 mL的高血压脑出血破入脑室患者行EVD联合开颅HE可同时清除幕上及脑室内血肿，较单纯EVD治疗疗效更佳。这与以往研究结果相似，例如Bhattathiri等[13]研究表明对脑出血破入脑室行开颅HE的患者预后优于保守治疗，但差异无统计学意义。Liu等[14]总结并分析了310例高血压脑出血患者资料，发现对于幕上血肿量≥30 mL、行手术治疗患者的术后死亡率低于保守治疗。Gaab等[15]认为对脑出血破入脑室患者同时行内镜下幕上及脑室内HE可改善患者预后。其机制可能为脑实质内血肿及血肿周边水肿的脑组织使颅内压增高，因脑脊液循环障碍而在一定程度上导致代偿性脑室扩大，而开颅HE会抵消这种代偿作用，使脑室内出血流动加快，更利于脑室内血肿的清除。

对于幕上血肿量＞30 mL的患者，EVD+HE组患者的NICU住院天数较EVD组更久，肺部感染率及颅内感染率也更高，但差异无统计学意义。去骨瓣减压术及开颅HE等传统手术需全身麻醉，直视下彻底清除血肿，止血充分，但对比局麻下就可进行的EVD操作烦琐，术前准备时间久。开放性手术暴露脑组织的时间长、范围广，既增加颅内感染的风险，也损伤正常脑组织，造成术后水肿反应明显[16]。幕上脑出血量较大的患者颅内占位效应明显，常伴意识不清、呕吐、自主呼吸减弱，易造成误吸而出现吸入性肺炎。既往文献报道颅脑手术、昏迷、机械通气、ICU住院等均与医院获得性肺炎相关[17]，也与本研究结果相近。

综上所述，对于高血压脑出血破入脑室患者，EVD联合开颅HE可作为单纯EVD的替代方案。对于幕上血肿量＞30 mL的患者行EVD联合开颅HE可改善患者预后，较单纯EVD疗效更佳。但本研究为回顾性研究，获取临床资料时受数据库等限制，信息偏倚及选择偏倚在所难免。不同主治医师对患者的治疗也存在偏差。本研究样本量较少，所得结论尚需更多的研究证实。

参考文献
[1] FEIGIN V L, LAWES C M, BENNETT D A, BARKER-COLLO S L, PARAG V. Worldwide stroke incidence and early case fatality reported in 56 population-based studies:a systematic review[J]. Lancet Neurol, 2009, 8: 355–369. DOI: 10.1016/S1474-4422(09)70025-0
[2] RAPSOMANIKI E, TIMMIS A, GEORGE J, PUJADES-RODRIGUEZ M, SHAH A D, DENAXAS S, et al. Blood pressure and incidence of twelve cardiovascular diseases:lifetime risks, healthy life-years lost, and age-specific associations in 1.25 million people[J]. Lancet, 2014, 383: 1899–1911. DOI: 10.1016/S0140-6736(14)60685-1
[3] STEINER T, AL-SHAHI SALMAN R, BEER R, CHRISTENSEN H, CORDONNIER C, CSIBA L, et al. European Stroke Organisation (ESO) guidelines for the management of spontaneous intracerebral hemorrhage[J]. Int J Stroke, 2014, 9: 840–855. DOI: 10.1111/ijs.12309
[4] CHAN E, ANDERSON C S, WANG X, ARIMA H, SAXENA A, MOULLAALI T J, et al. Significance of intraventricular hemorrhage in acute intracerebral hemorrhage:intensive blood pressure reduction in acute cerebral hemorrhage trial results[J]. Stroke, 2015, 46: 653–658. DOI: 10.1161/STROKEAHA.114.008470
[5] KHAN N R, TSIVGOULIS G, LEE S L, JONES G M, GREEN C S, KATSANOS A H, et al. Fibrinolysis for intraventricular hemorrhage:an updated meta-analysis and systematic review of the literature[J]. Stroke, 2014, 45: 2662–2669. DOI: 10.1161/STROKEAHA.114.005990
[6] HEMPHILL J C 3rd, GREENBERG S M, ANDERSON C S, BECKER K, BENDOK B R, CUSHMAN M, et al. Guidelines for the management of spontaneous intracerebral hemorrhage:a guideline for healthcare professionals from the American Heart Association/American Stroke Association[J]. Stroke, 2015, 46: 2032–2060. DOI: 10.1161/STR.0000000000000069
[7] CINIBULAK Z, ASCHOFF A, APEDJINOU A, KAMINSKY J, TROST H A, KRAUSS J K. Current practice of external ventricular drainage:a survey among neurosurgical departments in Germany[J]. Acta Neurochir, 2016, 158: 847–853. DOI: 10.1007/s00701-016-2747-y
[8] STAYKOV D, HUTTNER H B, STRUFFERT T, GANSLANDT O, DOERflER A, SCHWAB S, et al. Intraventricular fibrinolysis and lumbar drainage for ventricular hemorrhage[J]. Stroke, 2009, 40: 3275–3280. DOI: 10.1161/STROKEAHA.109.551945
[9] GABEREL T, MAGHERU C, EMERY E. Management of non-traumatic intraventricular hemorrhage[J]. Neurosurg Rev, 2012, 35: 485–494. DOI: 10.1007/s10143-012-0399-9
[10] MENDELOW A D, GREGSON B A, FERNANDES H M, MURRAY G D, TEASDALE G M, HOPE D T, et al. Early surgery versus initial conservative treatment in patients with spontaneous supratentorial intracerebral haematomas in the International Surgical Trial in Intracerebral Haemorrhage (STICH):a randomised trial[J]. Lancet, 2005, 365: 387–397. DOI: 10.1016/S0140-6736(05)70233-6
[11] KEEP R F, HUA Y, XI G. Intracerebral haemorrhage:mechanisms of injury and therapeutic targets[J]. Lancet Neurol, 2012, 11: 720–731. DOI: 10.1016/S1474-4422(12)70104-7
[12] ASADOLLAHI S, VAFAEI A, HEIDARI K. CT imaging for long-term functional outcome after spontaneous intracerebral haemorrhage:a 3-year follow-up study[J]. Brain Inj, 2016, 28: 1–9.
[13] BHATTATHIRI P S, GREGSON B, PRASAD K S, MENDELOW A D; STICH investigators. Intraventricular hemorrhage and hydrocephalus after spontaneous intracerebral hemorrhage:results from the STICH trial[J]. Acta Neurochir Suppl, 2006, 96: 65–68. DOI: 10.1007/3-211-30714-1
[14] LIU H, ZEN Y, LI J, WANG X, LI H, XU J, et al. Optimal treatment determination on the basis of haematoma volume and intra-cerebral haemorrhage score in patients with hypertensive putaminal haemorrhages:a retrospective analysis of 310 patients[J]. BMC Neurol, 2014, 14: 141. DOI: 10.1186/1471-2377-14-141
[15] GAAB M R. Intracerebral hemorrhage (ICH) and intraventricular hemorrhage (IVH):improvement of bad prognosis by minimally invasive neurosurgery[J]. World Neurosurg, 2011, 75: 206–208. DOI: 10.1016/j.wneu.2010.10.003
[16] MANNO E M, ATKINSON J L, FULGHAM J R, WIJDICKS E F. Emerging medical and surgical management strategies in the evaluation and treatment of intracerebral hemorrhage[J]. Mayo Clin Proc, 2005, 80: 420–433. DOI: 10.4065/80.3.420
[17] KALIL A C, METERSKY M L, KLOMPAS M, MUSCEDERE J, SWEENEY D A, PALMER L B, et al. Management of adults with hospital-acquired and ventilator-associated pneumonia:2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society[J/OL]. Clin Infect Dis, 2016, 63:e61-e111. doi:10.1093/cid/ciw353.